{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T04:26:39Z","timestamp":1787631999822,"version":"build-2736575974"},"reference-count":218,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Organization of the Laboratory for the Creation of anticancer drugs","award":["ALM-202310062530"],"award-info":[{"award-number":["ALM-202310062530"]}]},{"name":"Xinjiang International Science &amp; Technology Cooperation Key Program","award":["2025E01054"],"award-info":[{"award-number":["2025E01054"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The thieno[3,2-d]pyrimidine scaffolds have emerged as an important class of heterocycles in anticancer drug discovery, with clinically advanced drugs olmutinib and pictilisib highlighting their therapeutic potential. This review presents thieno[3,2-d]pyrimidine-containing anticancer agents reported between January 2008 and August 2025, focusing on synthetic methodologies, anticancer-related biological activities, and structure\u2013activity relationships. Thieno[3,2-d]pyrimidine derivatives have been investigated as inhibitors of numerous cancer-related targets, including EGFR, PI3K\/mTOR, CDKs, JAK, VEGFR, HDAC, ATR, and other oncogenic proteins. This review also summarizes thieno[3,2-d]pyrimidine scaffolds with anticancer activity, with particular emphasis on the design and synthesis of lead compounds, molecular hybridization strategies, and recent advances in this area. Synthetic pathways for lead compounds are systematically presented and discussed, along with pharmacophoric features. In addition, detailed structure\u2013activity relationship analyses are provided to highlight the influence of heterocyclic fusion, linker optimization, hydrogen-bonding motifs, electronic effects, hydrophobic fragments, and the introduction of hybrid scaffolds on antiproliferative potency, kinase inhibition, selectivity, and multitarget activity. In addition, this review demonstrates the significant potential of thieno[3,2-d]pyrimidine-based scaffolds as a privileged platform for the development of next-generation targeted anticancer agents and offers valuable guidance for future medicinal chemistry research.<\/jats:p>","DOI":"10.3390\/ijms27167457","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:05:19Z","timestamp":1787241919000},"page":"7457","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Thieno[3,2-d]pyrimidines in Anticancer Drug Discovery: Recent Advances in Drug Design and Molecular Targets"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1887-6804","authenticated-orcid":false,"given":"Anvarjon","family":"Buronov","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7753-4262","authenticated-orcid":false,"given":"Shukhrat","family":"Gaybullaev","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zarifa","family":"Murtazaeva","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feruza","family":"Ruzieva","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zohidjon","family":"Khushnazarov","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davron","family":"Turgunov","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azizbek","family":"Nasrullaev","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rustamkhon","family":"Kuryazov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Urgench State University named after Abu Rayhan Biruni, Kh. Olimjon st. 14, Urgench 220100, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5281-9446","authenticated-orcid":false,"given":"Yuldash","family":"Takhirov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Urgench State University named after Abu Rayhan Biruni, Kh. Olimjon st. 14, Urgench 220100, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firdavsi","family":"Tursunov","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Temur","family":"Kushatov","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7971-9752","authenticated-orcid":false,"given":"Dilshod","family":"Dushamov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Urgench State University named after Abu Rayhan Biruni, Kh. Olimjon st. 14, Urgench 220100, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shavkat","family":"Matmuratov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Urgench State University named after Abu Rayhan Biruni, Kh. Olimjon st. 14, Urgench 220100, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilufar","family":"Nurullaeva","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Urgench State University named after Abu Rayhan Biruni, Kh. Olimjon st. 14, Urgench 220100, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aziza","family":"Shodikulova","sequence":"additional","affiliation":[{"name":"Samarkand State Medical University, Amir Temur st. 18, Samarkand 140100, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kakhor","family":"Khalikov","sequence":"additional","affiliation":[{"name":"Samarkand State Medical University, Amir Temur st. 18, Samarkand 140100, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilafruz","family":"Kholmurodova","sequence":"additional","affiliation":[{"name":"Scientific and Practical Center of Immunology, Allergology and Human Genomics, Samarkand State Medical University, Makhd\u016bm-i A\u02bf\u1e93am st. 18, Samarkand 140104, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4597-4047","authenticated-orcid":false,"given":"Sodik","family":"Numonov","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, Uzbekistan"},{"name":"Research Institution \u201cChinese-Tajik Innovation Center for Natural Products\u201d, National Academy of Sciences of Tajikistan, Dushanbe 734063, Tajikistan"},{"name":"State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Rd 40-1, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5943-6771","authenticated-orcid":false,"given":"Chao","family":"Niu","sequence":"additional","affiliation":[{"name":"State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Rd 40-1, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Geriatric General Surgery, The Second Affiliated Hospital, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Rd 40-1, Urumqi 830011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2668-6974","authenticated-orcid":false,"given":"Zhishen","family":"Ge","sequence":"additional","affiliation":[{"name":"School of Chemistry, State Key Laboratory of Fluorine & Nitrogen Chemicals, Institute of New Concept Sensors and Molecular Materials (INCSMM), Engineering Research Center of Energy Storage Materials and Devices, Ministry of Education, Xi\u2019an Key Laboratory of Sustainable Polymer Materials, Xi\u2019an Jiaotong University, Xi\u2019an 710049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7449-0936","authenticated-orcid":false,"given":"Khurshed","family":"Bozorov","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Institute of Biochemistry, Samarkand State University, University Blvd. 15, Samarkand 140104, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1093\/annonc\/mdw604","article-title":"Causes of death among cancer patients","volume":"28","author":"Zaorsky","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e2200429","DOI":"10.1200\/GO.22.00429","article-title":"It Is Time to Close the Gap in Cancer Care","volume":"9","author":"Dunn","year":"2023","journal-title":"JCO Glob. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1007\/s11095-008-9661-9","article-title":"Cancer is a Preventable Disease that Requires Major Lifestyle Changes","volume":"25","author":"Anand","year":"2008","journal-title":"Pharm. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e14483","DOI":"10.1111\/acel.14483","article-title":"Aging and Cancer\u2014Inextricably Linked Across the Lifespan","volume":"24","author":"DeGregori","year":"2025","journal-title":"Aging Cell"},{"key":"ref_6","first-page":"223","article-title":"Nowcasting and forecasting global aging and cancer burden: Analysis of data from the GLOBOCAN and Global Burden of Disease Study","volume":"4","author":"Li","year":"2024","journal-title":"J. Natl. Cancer Cent."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1016\/j.amepre.2013.10.029","article-title":"Age and Cancer Risk: A Potentially Modifiable Relationship","volume":"46","author":"White","year":"2014","journal-title":"Am. J. Prev. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"21355","DOI":"10.1038\/s41598-024-66401-6","article-title":"Radiotherapy is recommended for hormone receptor-negative older breast cancer patients after breast conserving surgery","volume":"14","author":"Liu","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5146","DOI":"10.1038\/s41467-023-40844-3","article-title":"Immunotherapy targeting different immune compartments in combination with radiation therapy induces regression of resistant tumors","volume":"14","author":"Rudqvist","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Tian, H., Zhou, Q., Zheng, M., Cao, Y., Wang, Z., Ji, Y., Tskhovrebov, A.G., Bozorov, K., and Ge, Z. (2026). A dual-responsive polyzwitterionic nanoplatform enabling trisulfide-mediated synergistic chemodynamic and gas therapy for tumors. Chin. Chem. Lett., in press.","DOI":"10.1016\/j.cclet.2026.112612"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/s41416-024-02692-w","article-title":"The road to tailored adjuvant chemotherapy for all four non-pancreatic periampullary cancers: An international multimethod cohort study","volume":"131","author":"Uijterwijk","year":"2024","journal-title":"Br. J. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5413","DOI":"10.1038\/s41467-025-61222-1","article-title":"Role of stem-like cells in chemotherapy resistance and relapse in pediatric T-cell acute lymphoblastic leukemia","volume":"16","author":"Costea","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"114724","DOI":"10.1016\/j.addr.2023.114724","article-title":"Recent advances in long-acting drug delivery systems for anticancer drug","volume":"194","author":"Pacheco","year":"2023","journal-title":"Adv. Drug Del. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s12672-025-02198-8","article-title":"Advancements and limitations in traditional anti-cancer therapies: A comprehensive review of surgery, chemotherapy, radiation therapy, and hormonal therapy","volume":"16","author":"Zafar","year":"2025","journal-title":"Discov. Oncol."},{"key":"ref_15","first-page":"100281","article-title":"Advances in the delivery of anticancer drugs by nanoparticles and chitosan-based nanoparticles","volume":"8","year":"2024","journal-title":"Int. J. Pharm. X"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1021\/acs.bioconjchem.6c00021","article-title":"Cascade-Responsive Zwitterionic Polyprodrugs Leverage Fast Transcytosis for Deep Tumor Penetration and Intracellular Drug Release","volume":"37","author":"Cao","year":"2026","journal-title":"Bioconjugate Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/s41392-021-00572-w","article-title":"Small molecules in targeted cancer therapy: Advances, challenges, and future perspectives","volume":"6","author":"Zhong","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1016\/j.drudis.2022.02.015","article-title":"Small molecules and their impact in drug discovery: A perspective on the occasion of the 125th anniversary of the Bayer Chemical Research Laboratory","volume":"27","author":"Beck","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e181","DOI":"10.1002\/mco2.181","article-title":"Small molecule inhibitors targeting the cancers","volume":"3","author":"Liu","year":"2022","journal-title":"MedComm"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1158\/2159-8290.CD-23-0280","article-title":"Precision Oncology Comes of Age: Designing Best-in-Class Small Molecules by Integrating Two Decades of Advances in Chemistry, Target Biology, and Data Science","volume":"13","author":"Stuart","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"107860","DOI":"10.1016\/j.pharmthera.2021.107860","article-title":"Deciphering the key heterocyclic scaffolds in targeting microtubules, kinases and carbonic anhydrases for cancer drug development","volume":"225","author":"Peerzada","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Murtazaeva, Z., Nasrullaev, A., Buronov, A., Gaybullaev, S., Nie, L., Numonov, S., Khushnazarov, Z., Turgunov, D., Kuryazov, R., and Zhao, J. (2025). Imidazole Hybrids: A Privileged Class of Heterocycles in Medicinal Chemistry with New Insights into Anticancer Activity. Molecules, 30.","DOI":"10.3390\/molecules30102245"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"106506","DOI":"10.1016\/j.bioorg.2023.106506","article-title":"Discovery of novel (E)-1-methyl-9-(3-methylbenzylidene)-6,7,8,9-tetrahydropyrazolo[3,4-d]pyrido[1,2-a]pyrimidin-4(1H)-one as DDR2 kinase inhibitor: Synthesis, molecular docking, and anticancer properties","volume":"135","author":"Ruzi","year":"2023","journal-title":"Bioorg. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"118375","DOI":"10.1016\/j.bmc.2025.118375","article-title":"Aurone and its analogues as targeted drugs for the anticancer treatment","volume":"130","author":"Shi","year":"2025","journal-title":"Bioorg. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1134\/S1070428020090031","article-title":"Benzazoles: III. Synthesis and Transformations of 6-(Chlorosulfonyl)-1,3-benzothiazol-2(3H)-ones","volume":"56","author":"Dushamov","year":"2020","journal-title":"Russ. J. Org. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1007\/s10593-010-0458-5","article-title":"Quinazolines. 2*. unsymmetric 1,3-dialkyl-6-chlorosulfonyl- quinazoline-2,4-diones in nucleo- philic substitution reactions","volume":"45","author":"Kuryazov","year":"2009","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"116838","DOI":"10.1016\/j.ejmech.2024.116838","article-title":"Nitrogen-containing heterocyclic drug products approved by the FDA in 2023: Synthesis and biological activity","volume":"279","author":"Luo","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kumar, A., Singh, A.K., Singh, H., Vijayan, V., Kumar, D., Naik, J., Thareja, S., Yadav, J.P., Pathak, P., and Grishina, M. (2023). Nitrogen Containing Heterocycles as Anticancer Agents: A Medicinal Chemistry Perspective. Pharmaceuticals, 16.","DOI":"10.3390\/ph16020299"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11622","DOI":"10.1021\/acs.jmedchem.4c01122","article-title":"An Update on the Nitrogen Heterocycle Compositions and Properties of U.S. FDA-Approved Pharmaceuticals (2013\u20132023)","volume":"67","author":"Marshall","year":"2024","journal-title":"J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1021\/acs.jnatprod.5c01211","article-title":"Asymmetric Total Synthesis and Anti-Inflammatory Activity of Berbamine, Oxyacanthine, and Related Intermediates","volume":"88","author":"Xiang","year":"2025","journal-title":"J. Nat. Prod."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Turgunov, D., Nie, L., Nasrullaev, A., Murtazaeva, Z., Wang, B., Kholmurodova, D., Kuryazov, R., Zhao, J., Bozorov, K., and Aisa, H.A. (2025). Synthesis of Novel 7-Phenyl-2,3-Dihydropyrrolo[2,1-b]Quinazolin-9(1H)-ones as Cholinesterase Inhibitors Targeting Alzheimer\u2019s Disease Through Suzuki\u2013Miyaura Cross-Coupling Reaction. Molecules, 30.","DOI":"10.3390\/molecules30132791"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1002\/jhet.4863","article-title":"Design, synthesis, biological evaluation of a new tricyclicthiazolopy-rimidinone derivatives as acetylcholinesterase inhibitors","volume":"61","author":"Zeng","year":"2024","journal-title":"J. Heterocycl. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1002\/jhet.4791","article-title":"Synthesis of tricyclic pyrazolopyrimidine arylidene ester derivatives and their cytotoxic and molecular docking evaluations","volume":"61","author":"Lu","year":"2024","journal-title":"J. Heterocycl. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1055\/s-0037-1610157","article-title":"A Convenient One-pot Synthesis of 2,3-Disubstituted Thieno[2,3-d]pyrimidin-4(3H)-ones from 2H-Thieno[2,3-d][1,3]oxazine-2,4(1H)-diones, Aromatic Aldehydes and Amines","volume":"2","author":"Liu","year":"2018","journal-title":"SynOpen"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1007\/s11164-018-03731-x","article-title":"Synthesis, characterization, and antimicrobial activity of novel hydrazone-bearing tricyclic quinazolines","volume":"45","author":"Nasrullaev","year":"2019","journal-title":"Res. Chem. Intermed."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"41","DOI":"10.24820\/ark.5550190.p009.852","article-title":"Recent advances in ipso-nitration reactions","volume":"2017","author":"Bozorov","year":"2016","journal-title":"ARKIVOC"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1002\/jhet.4452","article-title":"Design, synthesis, in vitro evaluation of a new pyrrolo[1,2-a]thiazolo[5,4-d]pyrimidinone derivatives as cholinesterase inhibitors against Alzheimer\u2019s disease","volume":"59","author":"Zeng","year":"2022","journal-title":"J. Heterocycl. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1007\/s10593-011-0677-4","article-title":"Thieno[2,3-d]pyrimidin-4-ones 1. condensation of 2,3-dimethyl- and 2,3-tri-, 2,3-tetra-, and 2,3-pentamethylene-7,8-dihydro-pyrrolo[1,2-a]thieno[2,3-d]pyriminidin-4(6H)-ones with aromatic aldehydes and furfural","volume":"46","author":"Elmuradov","year":"2011","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6835","DOI":"10.1007\/s11164-017-3023-3","article-title":"Synthesis and biological evaluation of novel sulfonamide derivatives of tricyclic thieno[2,3-d]pyrimidin-4(3H)-ones on melanin synthesis in murine B16 cells","volume":"43","author":"Nie","year":"2017","journal-title":"Res. Chem. Intermed."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s10593-010-0549-3","article-title":"Quinazolines. 3*. synthesis of 6-bromo-8-chloro- sulfonylquinazoline- 2,4(1H,3H)-dione and its interaction with nucleophilic reagents","volume":"46","author":"Kuryazov","year":"2010","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1080\/10426507.2018.1487968","article-title":"Design, synthesis, and toward a side-ring optimization of tricyclic thieno[2,3-d]pyrimidin-4(3H)-ones and their effect on melanin synthesis in murine B16 cells","volume":"193","author":"Nie","year":"2018","journal-title":"Phosphorus Sulfur Silicon Relat. Elem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1515\/hc-2017-0256","article-title":"Diversity-oriented synthesis of amide derivatives of tricyclic thieno[2,3-d]pyrimidin-4(3H)-ones and evaluation of their influence on melanin synthesis in murine B16 cells","volume":"24","author":"Nie","year":"2018","journal-title":"Heterocycl. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/jhet.4401","article-title":"2-substituted tricyclic oxazolo[5,4-d]pyrimidine library: Design, synthesis, and cytotoxicity activity","volume":"59","author":"Zeng","year":"2022","journal-title":"J. Heterocycl. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"543","DOI":"10.6023\/cjoc202107002","article-title":"Synthesis and Biological Activities of Dihydrooxazolo[5,4-d]-pyrrolo[1,2-a]pyrimidinones","volume":"42","author":"Zeng","year":"2022","journal-title":"Chin. J. Org. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Song, B., Murtazaeva, Z., Nie, L., Kuryazov, R., Gaybullaev, S., Niu, C., Bozorov, K., Aisa, H.A., and Zhao, J. (2025). Pyrrolopyrimidines: Design, Synthesis and Antitumor Properties of Novel Tricyclic Pyrrolo [2,3-d]pyrimidine Derivatives. Molecules, 30.","DOI":"10.3390\/molecules30142917"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.3987\/COM-22-14652","article-title":"Synthesis and Antitumor Activity of Novel Linear Tricyclic Compounds Derived from Purine","volume":"104","author":"Guo","year":"2022","journal-title":"Heterocycles"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e2000470","DOI":"10.1002\/ardp.202000470","article-title":"Synthesis and anticancer activity of ethyl 5-amino-1-N-substituted-imidazole-4-carboxylate building blocks","volume":"354","author":"Ruzi","year":"2021","journal-title":"Arch. Pharm."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.6023\/cjoc202210040","article-title":"Synthesis of Diethyl 2,5-Diaminothiophene-3,4-dicarboxylate Derivatives and Antitumor Activity Study","volume":"43","author":"Zhang","year":"2023","journal-title":"Chin. J. Org. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"976715","DOI":"10.1155\/2013\/976715","article-title":"Synthesis of substituted thieno[2,3-d]pyrimidin-4-ones and their testing for evaluation of cytotoxic activity on mammalian cell models","volume":"2013","author":"Bozorov","year":"2013","journal-title":"J. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1007\/s11164-022-04912-5","article-title":"Parallel synthesis of condensed pyrimidine-thiones and their antitumor activities","volume":"49","author":"Song","year":"2023","journal-title":"Res. Chem. Intermed."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e202201059","DOI":"10.1002\/cbdv.202201059","article-title":"Furo[2,3-d]pyrimidines as Mackinazolinone\/Isaindigotone Analogs: Synthesis, Modification, Antitumor Activity, and Molecular Docking Study","volume":"20","author":"Song","year":"2023","journal-title":"Chem. Biodivers."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1007\/s11030-022-10529-y","article-title":"Design, combinatorial synthesis and cytotoxic activity of 2-substituted furo[2,3-d]pyrimidinone and pyrrolo[2,3-d]pyrimidinone library","volume":"27","author":"Song","year":"2023","journal-title":"Mol. Divers."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.4155\/fmc-2023-0207","article-title":"Pyrazole: An Emerging Privileged Scaffold in Drug Discovery","volume":"15","author":"Alam","year":"2023","journal-title":"Future Med. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"116715","DOI":"10.1016\/j.ejmech.2024.116715","article-title":"Novel tetrasubstituted 5-Arylamino pyrazoles able to interfere with angiogenesis and Ca2+ mobilization","volume":"276","author":"Lusardi","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"115955","DOI":"10.1016\/j.ejmech.2023.115955","article-title":"Discovery and optimization of thieno[3,2-d]pyrimidine derivatives as highly selective inhibitors of cyclin-dependent kinase 7","volume":"263","author":"Zhang","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e202302071","DOI":"10.1002\/cbdv.202302071","article-title":"In silico Design, Synthesis and Biological Evaluation of Novel Thieno[3,2-d]pyrimidine Derivatives for Cancer Therapy\u2014A Preliminary Study on the Inhibitory Potential towards ATR Kinase Domain and PIKK Family","volume":"21","author":"Sirakanyan","year":"2024","journal-title":"Chem. Biodivers."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3519","DOI":"10.1002\/cncr.30286","article-title":"A multicenter, single-arm, open-label, phase 2 study of apitolisib (GDC-0980) for the treatment of recurrent or persistent endometrial carcinoma (MAGGIE study)","volume":"122","author":"Makker","year":"2016","journal-title":"Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2874","DOI":"10.1158\/1078-0432.CCR-15-2225","article-title":"Study of Apitolisib (GDC-0980), Dual Phosphatidylinositol-3-Kinase and Mammalian Target of Rapamycin Kinase Inhibitor, in Patients with Advanced Solid Tumors","volume":"22","author":"Dolly","year":"2016","journal-title":"Clin. Cancer. Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Omeljaniuk, W.J., Kr\u0119towski, R., Ratajczak-Wrona, W., Jab\u0142o\u0144ska, E., and Cechowska-Pasko, M. (2021). Novel Dual PI3K\/mTOR Inhibitor, Apitolisib (GDC-0980), Inhibits Growth and Induces Apoptosis in Human Glioblastoma Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111511"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1016\/j.bbrc.2020.06.011","article-title":"GDC-0980 (apitolisib) treatment with gemcitabine and\/or cisplatin synergistically reduces cholangiocarcinoma cell growth by suppressing the PI3K\/Akt\/mTOR pathway","volume":"529","author":"Jang","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s40268-024-00459-5","article-title":"Retrospective Assessment of Translational Pharmacokinetic\u2013Pharmacodynamic Modeling Performance: A Case Study with Apitolisib, a Dual PI3K\/mTOR Inhibitor","volume":"24","author":"Moein","year":"2024","journal-title":"Drugs R&D"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.tips.2005.02.007","article-title":"The efficiency of multi-target drugs: The network approach might help drug design","volume":"26","author":"Csermely","year":"2005","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"105208","DOI":"10.1016\/j.bioorg.2021.105208","article-title":"New thieno[3,2-d]pyrimidine-based derivatives: Design, synthesis and biological evaluation as antiproliferative agents, EGFR and ARO inhibitors inducing apoptosis in breast cancer cells","volume":"115","author":"Farghaly","year":"2021","journal-title":"Bioorg. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1158\/1535-7163.MCT-15-0815","article-title":"Plasma Metabolomic Changes following PI3K Inhibition as Pharmacodynamic Biomarkers: Preclinical Discovery to Phase I Trial Evaluation","volume":"15","author":"Ang","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s10637-019-00776-6","article-title":"Phase Ib study of the MEK inhibitor cobimetinib (GDC-0973) in combination with the PI3K inhibitor pictilisib (GDC-0941) in patients with advanced solid tumors","volume":"38","author":"Shapiro","year":"2020","journal-title":"Investig. New Drugs"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1158\/1078-0432.CCR-14-0947","article-title":"First-in-Human Phase I Study of Pictilisib (GDC-0941), a Potent Pan\u2013Class I Phosphatidylinositol-3-Kinase (PI3K) Inhibitor, in Patients with Advanced Solid Tumors","volume":"21","author":"Sarker","year":"2015","journal-title":"Clin. Cancer. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1200\/JCO.2015.64.8808","article-title":"Randomized Open-Label Phase II Trial of Apitolisib (GDC-0980), a Novel Inhibitor of the PI3K\/Mammalian Target of Rapamycin Pathway, Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma","volume":"34","author":"Powles","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.jpba.2014.08.001","article-title":"A supported liquid extraction-LC\u2013MS\/MS method for determination of GDC-0980 (Apitolisib), a dual small-molecule inhibitor of class 1A phosphoinositide 3-kinase and mammalian target of rapamycin, in human plasma","volume":"100","author":"Ding","year":"2014","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1002\/bmc.3417","article-title":"Determination of GDC-0980 (apitolisib), a small molecule dual phosphatidylinositide 3-kinase\/mammalian target of rapamycin inhibitor in dog plasma by LC-MS\/MS to support a GLP toxicology study","volume":"29","author":"Ding","year":"2015","journal-title":"Biomed. Chromatogr."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"110343","DOI":"10.1016\/j.cbi.2023.110343","article-title":"PI3K \u03b4 inhibitor PI-3065 induces apoptosis in hepatocellular carcinoma cells by targeting survivin","volume":"371","author":"Wei","year":"2023","journal-title":"Chem. Biol. Interact."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/s41416-021-01285-1","article-title":"Sequential targeting of PI3K\u03b4 and LAG3 as an effective anti-cancer approach","volume":"125","author":"Lauder","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nature13444","article-title":"Inactivation of PI(3)K p110\u03b4 breaks regulatory T-cell-mediated immune tolerance to cancer","volume":"510","author":"Ali","year":"2014","journal-title":"Nature"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"16617","DOI":"10.1002\/anie.201907632","article-title":"Discovery of the Hedgehog Pathway Inhibitor Pipinib that Targets PI4KIII\u00df","volume":"58","author":"Kremer","year":"2019","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1007\/s40265-016-0606-z","article-title":"Olmutinib: First Global Approval","volume":"76","author":"Kim","year":"2016","journal-title":"Drugs"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1158\/2767-9764.CRC-22-0277","article-title":"Safety, Tolerability, and Pharmacokinetics of TAK-931, a Cell Division Cycle 7 Inhibitor, in Patients with Advanced Solid Tumors: A Phase I First-in-Human Study","volume":"2","author":"Kuboki","year":"2022","journal-title":"Cancer Res. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/s41420-022-00877-x","article-title":"CDC7 kinase (DDK) inhibition disrupts DNA replication leading to mitotic catastrophe in Ewing sarcoma","volume":"8","author":"Martin","year":"2022","journal-title":"Cell Death Discov."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"115254","DOI":"10.1016\/j.bmc.2019.115254","article-title":"Synthesis and biological activity of thieno[3,2-d]pyrimidines as potent JAK3 inhibitors for the treatment of idiopathic pulmonary fibrosis","volume":"28","author":"Zhu","year":"2020","journal-title":"Biorg. Med. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1007\/s00280-009-1076-8","article-title":"SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing flexibility in vivo","volume":"65","author":"Arbitrario","year":"2010","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1158\/1535-7163.MCT-08-0754","article-title":"The Aurora kinase inhibitor SNS-314 shows broad therapeutic potential with chemotherapeutics and synergy with microtubule-targeted agents in a colon carcinoma model","volume":"8","author":"VanderPorten","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"14642","DOI":"10.1200\/jco.2008.26.15_suppl.14642","article-title":"Phase 1 trial of SNS-314, a novel selective inhibitor of aurora kinases A, B, and C, in advanced solid tumor patients","volume":"26","author":"Robert","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"107985","DOI":"10.1016\/j.bioorg.2024.107985","article-title":"Advances in structural identification of some thieno[2,3-d]pyrimidine scaffolds as antitumor molecules: Synthetic approaches and control programmed cancer cell death potential","volume":"154","author":"Mghwary","year":"2025","journal-title":"Bioorg. Chem."},{"key":"ref_82","first-page":"565","article-title":"Recent advances in thienopyrimidine chemistry: Synthesis and therapeutic exploration of their derivatives (2018\u20132025)","volume":"14","author":"Priya","year":"2025","journal-title":"World J. Pharm. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/j.bmc.2019.02.044","article-title":"Thieno[2,3-d]pyrimidine as a promising scaffold in medicinal chemistry: Recent advances","volume":"27","author":"Ali","year":"2019","journal-title":"Biorg. Med. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.ejmech.2015.08.018","article-title":"Recent developments regarding the use of thieno[2,3-d]pyrimidin-4-one derivatives in medicinal chemistry, with a focus on their synthesis and anticancer properties","volume":"102","author":"Bozorov","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2400125","DOI":"10.1002\/ardp.202400125","article-title":"Medicinal attributes of thienopyrimidine scaffolds incorporating the aryl urea motif as potential anticancer candidates via VEGFR inhibition","volume":"357","author":"Farag","year":"2024","journal-title":"Arch. Pharm."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e70146","DOI":"10.1111\/cbdd.70146","article-title":"Thienopyrimidine: Unveiling the Versatile Potential of a Promising Heterocyclic Scaffold in Drug Discovery","volume":"105","author":"Nadar","year":"2025","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1700242","DOI":"10.1002\/ardp.201700242","article-title":"Medicinal Attributes of Thienopyrimidine Based Scaffold Targeting Tyrosine Kinases and Their Potential Anticancer Activities","volume":"350","author":"Ghith","year":"2017","journal-title":"Arch. Pharm."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"16976","DOI":"10.1039\/D6RA00792A","article-title":"Recent green approaches for the synthesis of thienopyrimidine scaffolds: An overview (2007\u20132025)","volume":"16","author":"Rabeh","year":"2026","journal-title":"RSC Adv."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"118109","DOI":"10.1016\/j.bmc.2025.118109","article-title":"Thienopyrimidine: A promising scaffold in the development of kinase inhibitors with anticancer activities","volume":"121","author":"Liu","year":"2025","journal-title":"Biorg. Med. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s00044-023-03040-y","article-title":"Recent updates on thienopyrimidine derivatives as anticancer agents","volume":"32","author":"Sayed","year":"2023","journal-title":"Med. Chem. Res."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Lagard\u00e8re, P., Fersing, C., Masurier, N., and Lisowski, V. (2022). Thienopyrimidine: A Promising Scaffold to Access Anti-Infective Agents. Pharmaceuticals, 15.","DOI":"10.3390\/ph15010035"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.2174\/1389450122666210526094047","article-title":"Therapeutic Potential, Synthesis, Patent Evaluation and SAR Studies of Thieno[3,2-d]pyrimidine Derivatives: Recent Updates","volume":"22","author":"Islam","year":"2021","journal-title":"Curr. Drug Targets"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nrclinonc.2010.97","article-title":"Understanding resistance to EGFR inhibitors\u2014Impact on future treatment strategies","volume":"7","author":"Wheeler","year":"2010","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/ncponc0341","article-title":"EGFR inhibitors: What have we learned from the treatment of lung cancer?","volume":"2","author":"Giaccone","year":"2005","journal-title":"Nat. Clin. Pract. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/ni0403-313","article-title":"The role of PI3K in immune cells","volume":"4","author":"Koyasu","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/s43018-021-00218-4","article-title":"The present and future of PI3K inhibitors for cancer therapy","volume":"2","author":"Castel","year":"2021","journal-title":"Nat. Cancer"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41392-024-02080-z","article-title":"Cyclin-dependent protein kinases and cell cycle regulation in biology and disease","volume":"10","author":"Pellarin","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/s41698-025-00931-8","article-title":"Targeting CDKs in cancer therapy: Advances in PROTACs and molecular glues","volume":"9","author":"Marei","year":"2025","journal-title":"npj Precis. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nrc1317","article-title":"Microtubules as a target for anticancer drugs","volume":"4","author":"Jordan","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"eade8520","DOI":"10.1126\/science.ade8520","article-title":"JAK inhibition enhances checkpoint blockade immunotherapy in patients with Hodgkin lymphoma","volume":"384","author":"Zak","year":"2024","journal-title":"Science"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/s41392-025-02493-4","article-title":"mTOR signaling networks: Mechanistic insights and translational frontiers in disease therapeutics","volume":"10","author":"Zhang","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_103","first-page":"2413","article-title":"Inhibition of Cancer Cell Growth by Calcium Channel Antagonists in the Athymic Mouse1","volume":"52","author":"Taylor","year":"1992","journal-title":"Cancer Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"711","DOI":"10.2174\/1389450116666150309115922","article-title":"Heterocyclic Scaffolds: Centrality in Anticancer Drug Development","volume":"16","author":"Ali","year":"2015","journal-title":"Curr. Drug Targets"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"16852","DOI":"10.3390\/molecules200916852","article-title":"Heterocyclic Anticancer Compounds: Recent Advances and the Paradigm Shift towards the Use of Nanomedicine\u2019s Tool Box","volume":"20","author":"Martins","year":"2015","journal-title":"Molecules"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"369","DOI":"10.2174\/0115734064278334231211054053","article-title":"Nitrogen-fused Heterocycles: Empowering Anticancer Drug Discovery","volume":"20","author":"Biswas","year":"2024","journal-title":"Med. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1002\/jhet.3810","article-title":"Synthesis and antitumor evaluation of some new derivatives and fused heterocyclic compounds derived from thieno[2,3-b]pyridine: Part 2","volume":"57","author":"Hassan","year":"2020","journal-title":"J. Heterocycl. Chem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"719","DOI":"10.3184\/174751915X14474391581067","article-title":"Synthesis and Characterisation of Some Novel Fused Thiazolo[3,2-A] Pyrimidinones and Pyrimido[2,1-B][1,3]Thiazinones","volume":"39","author":"Abbas","year":"2015","journal-title":"J. Chem. Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1039\/C7QI00694B","article-title":"Efficient procedure with new fused pyrimidinone derivatives, Schiff base ligand and its La and Gd complexes by green chemistry","volume":"5","author":"Aly","year":"2018","journal-title":"Inorg. Chem. Front."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1016\/j.bmc.2014.02.033","article-title":"Antiproliferative activities of halogenated thieno[3,2-d]pyrimidines","volume":"22","author":"Temburnikar","year":"2014","journal-title":"Biorg. Med. Chem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1016\/j.bmc.2012.03.004","article-title":"Synthesis and biological evaluation of a series of thieno-expanded tricyclic purine 2\u2032-deoxy nucleoside analogues","volume":"20","author":"Wauchope","year":"2012","journal-title":"Biorg. Med. Chem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1248\/cpb.c13-00089","article-title":"Synthesis of Some Novel Thieno[3,2-d]pyrimidines as Potential Cytotoxic Small Molecules against Breast Cancer","volume":"61","author":"Kandeel","year":"2013","journal-title":"Chem. Pharm. Bull."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1007\/s12272-012-1107-6","article-title":"Synthesis and anticancer activity of some novel fused pyridine ring system","volume":"35","author":"Elansary","year":"2012","journal-title":"Arch. Pharmacal Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"135236","DOI":"10.1016\/j.molstruc.2023.135236","article-title":"New thieno[2,3-b]pyridine-fused pyrimidin-4(3H)-ones as potential thymidylate synthase inhibitors: Synthesis, SAR, in vitro and in silico study","volume":"1282","author":"Sanad","year":"2023","journal-title":"J. Mol. Struct."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1021\/jm300016v","article-title":"Potent and Selective Aminopyrimidine-Based B-Raf Inhibitors with Favorable Physicochemical and Pharmacokinetic Properties","volume":"55","author":"Mathieu","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"135952","DOI":"10.1016\/j.molstruc.2023.135952","article-title":"New pyrimidinothiophene derivatives: Synthesis, spectroscopic analysis, X-ray, DFT calculation, biological activity studies and ADMET prediction","volume":"1290","author":"Ding","year":"2023","journal-title":"J. Mol. Struct."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2164993","DOI":"10.1080\/16583655.2023.2164993","article-title":"Synthesis, molecular modelling and biological evaluation of new 4-aminothiophene and thienopyrimidine compounds","volume":"17","author":"Hossan","year":"2023","journal-title":"J. Taibah Univ. Sci."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Hu, Z., Shen, Q., Chen, Y., and Lu, W. (2017). Design, Synthesis and Anti-Proliferative Activities of 2,6-Substituted Thieno[3,2-d]pyrimidine Derivatives Containing Electrophilic Warheads. Molecules, 22.","DOI":"10.3390\/molecules22050788"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1007\/s00044-016-1703-y","article-title":"Design, synthesis and biological evaluation of novel thiophene and theinopyrimidine derivatives as anticancer agents","volume":"25","author":"Labib","year":"2016","journal-title":"Med. Chem. Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.ejmech.2013.05.012","article-title":"An unexpected Dimroth rearrangement leading to annelated thieno[3,2-d][1,2,3]triazolo[1,5-a]pyrimidines with potent antitumor activity","volume":"65","author":"Lauria","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ejmech.2012.09.002","article-title":"Design, synthesis and 3D-QSAR analysis of novel 2-hydrazinyl-4-morpholinothieno[3,2-d]pyrimidine derivatives as potential antitumor agents","volume":"57","author":"Zhu","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1248\/cpb.c12-00342","article-title":"Design, synthesis and anticancer activity of 4-morpholinothieno[3,2-d]pyrimidine derivatives bearing arylmethylene hydrazine moiety","volume":"60","author":"Zhu","year":"2012","journal-title":"Chem. Pharm. Bull."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1055\/s-0030-1258432","article-title":"Synthesis and Characterization of Substituted Pyrazino[2\u2032,3\u2032:4,5]thieno[3,2-d]pyrimidines and Related Molecules","volume":"2011","author":"Peinador","year":"2011","journal-title":"Synthesis"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"4782","DOI":"10.1039\/b915274a","article-title":"Direct metallation of thienopyrimidines using a mixed lithium\u2013cadmium base and antitumor activity of functionalized derivatives","volume":"7","author":"Lassagne","year":"2009","journal-title":"Org. Biomol. Chem."},{"key":"ref_125","first-page":"187","article-title":"Role of epidermal growth factor receptor in lung cancer and targeted therapies","volume":"7","author":"Liu","year":"2017","journal-title":"Am. J. Cancer Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"7242","DOI":"10.1158\/1078-0432.CCR-06-0646","article-title":"Molecular Mechanisms of Epidermal Growth Factor Receptor (EGFR) Activation and Response to Gefitinib and Other EGFR-Targeting Drugs","volume":"12","author":"Ono","year":"2006","journal-title":"Clin. Cancer. Res."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Zubair, T., and Bandyopadhyay, D. (2023). Small Molecule EGFR Inhibitors as Anti-Cancer Agents: Discovery, Mechanisms of Action, and Opportunities. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032651"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.apsb.2015.07.001","article-title":"Mechanisms of resistance to EGFR tyrosine kinase inhibitors","volume":"5","author":"Huang","year":"2015","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"103811","DOI":"10.1016\/j.bioorg.2020.103811","article-title":"A review on progression of epidermal growth factor receptor (EGFR) inhibitors as an efficient approach in cancer targeted therapy","volume":"99","author":"Ayati","year":"2020","journal-title":"Bioorg. Chem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"e202300634","DOI":"10.1002\/cmdc.202300634","article-title":"Insights into the Overcoming EGFRDel19\/T790M\/C797S Mutation: A Perspective on the 2-Aryl-4-aminothienopyrimidine Backbone","volume":"19","author":"Zhang","year":"2024","journal-title":"ChemMedChem"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"27774","DOI":"10.34172\/bi.2023.27774","article-title":"Synthesis and initial in vitro evaluation of olmutinib derivatives as prospective imaging probe for non-small cell lung cancer","volume":"14","author":"Fawwaz","year":"2024","journal-title":"Bioimpacts"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"112511","DOI":"10.1016\/j.ejmech.2020.112511","article-title":"Design, synthesis and antitumor activity of novel thiophene-pyrimidine derivatives as EGFR inhibitors overcoming T790M and L858R\/T790M mutations","volume":"203","author":"Xiao","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"112388","DOI":"10.1016\/j.ejmech.2020.112388","article-title":"Discovery of new thieno[3,2-d]pyrimidine derivatives targeting EGFRL858R\/T790M NSCLCs by the conformation constrained strategy","volume":"199","author":"Chen","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2205605","DOI":"10.1080\/14756366.2023.2205605","article-title":"Design, synthesis, and biological evaluation of pyrido[2,3-d]pyrimidine and thieno[2,3-d]pyrimidine derivatives as novel EGFRL858R\/T790M inhibitors","volume":"38","author":"Fu","year":"2023","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1248\/cpb.c15-00592","article-title":"Discovery of Potent Antiproliferative Agents Targeting EGFR Tyrosine Kinase Based on the Pyrido[3\u2032,2\u2032:4,5]thieno[3,2-d]pyrimidin-4-amine Scaffold","volume":"63","author":"Aziz","year":"2015","journal-title":"Chem. Pharm. Bull."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1111\/j.1747-0285.2010.01008.x","article-title":"Design, Synthesis, Docking and Antitumor Activity of Quinazolino [3, 4-a] thieno [3, 2-d] pyrimidin-8-one Derivatives","volume":"76","author":"Zheng","year":"2010","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"117052","DOI":"10.1016\/j.bmc.2022.117052","article-title":"Design, synthesis, and biological evaluation of 2-arylamino-4-(piperidin-4-yloxy)pyrimidines as potent EGFRT790M\/L858R inhibitors to treat non-small cell lung cancer","volume":"74","author":"Tian","year":"2022","journal-title":"Biorg. Med. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ctrv.2017.07.005","article-title":"Phosphoinositide 3-kinase (PI3K) pathway inhibitors in solid tumors: From laboratory to patients","volume":"59","author":"Janku","year":"2017","journal-title":"Cancer Treat. Rev."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s12943-024-02072-1","article-title":"Targeting PI3K family with small-molecule inhibitors in cancer therapy: Current clinical status and future directions","volume":"23","author":"Li","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"117671","DOI":"10.1016\/j.ejmech.2025.117671","article-title":"Design, synthesis and biological evaluation of novel 4-(thieno[3,2-d]pyrimidin-4-yl)morpholine derivatives as potent antitumor agents","volume":"293","author":"Liu","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"ref_141","first-page":"101028","article-title":"PI3K inhibitors: Efficacy in diverse cancer forms","volume":"45","author":"kianfar","year":"2025","journal-title":"Cancer Treat. Res. Commun."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"9228","DOI":"10.1021\/acs.jmedchem.6b01169","article-title":"Discovery of Orally Efficacious Phosphoinositide 3-Kinase \u03b4 Inhibitors with Improved Metabolic Stability","volume":"59","author":"Patel","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1038\/aps.2015.71","article-title":"PI3K isoform-selective inhibitors: Next-generation targeted cancer therapies","volume":"36","author":"Wang","year":"2015","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"127479","DOI":"10.1016\/j.bmcl.2020.127479","article-title":"Design, synthesis and structure-activity relationship study of piperazinone-containing thieno[3,2-d]pyrimidine derivatives as new PI3K\u03b4 inhibitors","volume":"30","author":"Wang","year":"2020","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Mishra, R., Patel, H., Alanazi, S., Kilroy, M.K., and Garrett, J.T. (2021). PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073464"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"100046","DOI":"10.1016\/j.clnves.2025.100046","article-title":"The mechanism of AKT activation in cancer","volume":"1","author":"Meng","year":"2025","journal-title":"Cell Investig."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Peng, Y., Wang, Y., Zhou, C., Mei, W., and Zeng, C. (2022). PI3K\/Akt\/mTOR Pathway and Its Role in Cancer Therapeutics: Are We Making Headway?. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.819128"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"103796","DOI":"10.1016\/j.bioorg.2020.103796","article-title":"Design, synthesis and biological evaluation of novel 2,4-bismorpholinothieno[3,2-d]pyrimidine and 2-morpholinothieno[3,2-d]pyrimidinone derivatives as potent antitumor agents","volume":"99","author":"Ye","year":"2020","journal-title":"Bioorg. Chem."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"103086","DOI":"10.1016\/j.bioorg.2019.103086","article-title":"Design, synthesis and biological evaluation of novel thieno[3,2-d]pyrimidine and quinazoline derivatives as potent antitumor agents","volume":"90","author":"Hu","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.ejmech.2014.07.099","article-title":"Design, synthesis and biological evaluation of novel thieno[3,2-d]pyrimidine derivatives containing diaryl urea moiety as potent antitumor agents","volume":"85","author":"Liu","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1021\/acs.jmedchem.6b01801","article-title":"Design and Elaboration of a Tractable Tricyclic Scaffold To Synthesize Druglike Inhibitors of Dipeptidyl Peptidase-4 (DPP-4), Antagonists of the C\u2013C Chemokine Receptor Type 5 (CCR5), and Highly Potent and Selective Phosphoinositol-3 Kinase \u03b4 (PI3K\u03b4) Inhibitors","volume":"60","author":"Schwehm","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"8007","DOI":"10.1021\/jm300867c","article-title":"The Design and Identification of Brain Penetrant Inhibitors of Phosphoinositide 3-Kinase \u03b1","volume":"55","author":"Heffron","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"34653","DOI":"10.1038\/srep34653","article-title":"A Novel Resveratrol Based Tubulin Inhibitor Induces Mitotic Arrest and Activates Apoptosis in Cancer Cells","volume":"6","author":"Thomas","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"118112","DOI":"10.1016\/j.ejmech.2025.118112","article-title":"Verubulin and its derivatives: Progress and promise in tubulin-targeted cancer therapy","volume":"300","author":"Mousavi","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"116791","DOI":"10.1016\/j.ejmech.2024.116791","article-title":"Discovery of novel thiophene[3,2-d]pyrimidine-based tubulin inhibitors with enhanced antitumor efficacy for combined use with anti-pd-l1 immunotherapy in melanoma","volume":"277","author":"Xu","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"116649","DOI":"10.1016\/j.ejmech.2024.116649","article-title":"Discovery and mechanistic insights into thieno[3,2-d]pyrimidine and heterocyclic fused pyrimidines inhibitors targeting tubulin for cancer therapy","volume":"276","author":"Wu","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"111679","DOI":"10.1016\/j.ejmech.2019.111679","article-title":"Design and synthesis of (2-(phenylamino)thieno[3,2-d]pyrimidin-4-yl)(3,4,5-trimethoxyphenyl)methanone analogues as potent anti-tubulin polymerization agents","volume":"183","author":"Tian","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/s41419-023-06246-5","article-title":"A novel c-Met\/TRK inhibitor 1D228 efficiently inhibits tumor growth by targeting angiogenesis and tumor cell proliferation","volume":"14","author":"An","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.bioorg.2018.01.037","article-title":"Discovery of thinopyrimidine-triazole conjugates as c-Met targeting and apoptosis inducing agents","volume":"77","author":"Wang","year":"2018","journal-title":"Bioorg. Chem."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.bmc.2017.11.039","article-title":"Synthesis and bioevaluation study of novel N-methylpicolinamide and thienopyrimidine derivatives as selectivity c-Met kinase inhibitors","volume":"26","author":"Wang","year":"2018","journal-title":"Biorg. Med. Chem."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.pharmthera.2014.12.001","article-title":"ATM and ATR as therapeutic targets in cancer","volume":"149","author":"Weber","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Mavroeidi, D., Georganta, A., Panagiotou, E., Syrigos, K., and Souliotis, V.L. (2024). Targeting ATR Pathway in Solid Tumors: Evidence of Improving Therapeutic Outcomes. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202401.1750.v1"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"115370","DOI":"10.1016\/j.ejmech.2023.115370","article-title":"Discovery of Thieno[3,2-d]pyrimidine derivatives as potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) kinase","volume":"255","author":"Duan","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1080\/00304948.2024.2316449","article-title":"Design, Synthesis, Anticancer Evaluation and Molecular Docking Studies of Amide Derivatives of Thienopyrimidine Isoxazoles","volume":"56","author":"Rangaswamy","year":"2024","journal-title":"Org. Prep. Proced. Int."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1021\/acs.jmedchem.7b01091","article-title":"Discovery of Novel Potent VEGFR-2 Inhibitors Exerting Significant Antiproliferative Activity against Cancer Cell Lines","volume":"61","author":"Zhang","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"107278","DOI":"10.1016\/j.bioorg.2024.107278","article-title":"Recent development of VEGFR small molecule inhibitors as anticancer agents: A patent review (2021\u20132023)","volume":"146","author":"Zeng","year":"2024","journal-title":"Bioorg. Chem."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"165","DOI":"10.4161\/mabs.2.2.11360","article-title":"The VEGF family in cancer and antibody-based strategies for their inhibition","volume":"2","author":"Sullivan","year":"2010","journal-title":"mAbs"},{"key":"ref_168","first-page":"1","article-title":"Discovery of novel tricyclic pyrido[3\u2032,2\u2032:4,5]thieno[3,2-d]pyrimidin-4-amine derivatives as VEGFR-2 inhibitors","volume":"60","author":"Said","year":"2015","journal-title":"Bioorg. Chem."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.ejmech.2013.03.022","article-title":"Design, synthesis and biological evaluation of new classes of thieno[3,2-d]pyrimidinone and thieno[1,2,3]triazine as inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2)","volume":"63","author":"Perspicace","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1021\/jm990256j","article-title":"Cyclin-Dependent Kinase Inhibitors:\u2009 Useful Targets in Cell Cycle Regulation","volume":"43","author":"Sielecki","year":"2000","journal-title":"J. Med. Chem."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1124\/mol.115.099325","article-title":"Cyclin-Dependent Kinase Inhibitors as Anticancer Therapeutics","volume":"88","author":"Law","year":"2015","journal-title":"Mol. Pharmacol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"107456","DOI":"10.1016\/j.bioorg.2024.107456","article-title":"Design, synthesis and evaluation of thieno[3,2-d]pyrimidine derivatives as novel potent CDK7 inhibitors","volume":"148","author":"Zhang","year":"2024","journal-title":"Bioorg. Chem."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1002\/jcb.22185","article-title":"Histone deacetylase inhibitors: Potential in cancer therapy","volume":"107","author":"Marks","year":"2009","journal-title":"J. Cell. Biochem."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1080\/14737140.2025.2452338","article-title":"Anticancer properties of histone deacetylase inhibitors\u2014What is their potential?","volume":"25","author":"Szwedkowicz","year":"2025","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"113825","DOI":"10.1016\/j.ejmech.2021.113825","article-title":"Combining histone deacetylase inhibitors (HDACis) with other therapies for cancer therapy","volume":"226","author":"Zhou","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.ejmech.2017.01.035","article-title":"Design, synthesis and biological evaluation of thienopyrimidine hydroxamic acid based derivatives as structurally novel histone deacetylase (HDAC) inhibitors","volume":"128","author":"Wang","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.bmc.2013.11.021","article-title":"Synthesis and anticancer activities of thieno[3,2-d]pyrimidines as novel HDAC inhibitors","volume":"22","author":"Tan","year":"2014","journal-title":"Biorg. Med. Chem."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"0747","DOI":"10.34133\/research.0747","article-title":"Advancements in Protein Kinase Inhibitors: From Discovery to Clinical Applications","volume":"8","author":"Baldi","year":"2025","journal-title":"Research"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"107696","DOI":"10.1016\/j.bioorg.2024.107696","article-title":"Therapeutic potential of anticancer activity of nitrogen-containing heterocyclic scaffolds as Janus kinase (JAK) inhibitor: Biological activity, selectivity, and structure\u2013activity relationship","volume":"152","author":"Pal","year":"2024","journal-title":"Bioorg. Chem."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"117308","DOI":"10.1016\/j.ejmech.2025.117308","article-title":"Identification of Thieno[3,2-d]pyrimidine derivatives as potent and selective Janus Kinase 1 inhibitors","volume":"286","author":"Kim","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"103542","DOI":"10.1016\/j.bioorg.2019.103542","article-title":"JAK3 inhibitors based on thieno[3,2-d]pyrimidine scaffold: Design, synthesis and bioactivity evaluation for the treatment of B-cell lymphoma","volume":"95","author":"Chi","year":"2020","journal-title":"Bioorg. Chem."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1186\/s12964-024-01607-9","article-title":"Potentials and future perspectives of multi-target drugs in cancer treatment: The next generation anti-cancer agents","volume":"22","author":"Doostmohammadi","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.2174\/1568026617666170707124126","article-title":"Multi-Targeted Anticancer Agents","volume":"17","author":"Zheng","year":"2017","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.ejmech.2017.10.021","article-title":"Dual or multi-targeting inhibitors: The next generation anticancer agents","volume":"143","author":"Raghavendra","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Nouri, Z., Fakhri, S., Nouri, K., Wallace, C.E., Farzaei, M.H., and Bishayee, A. (2020). Targeting Multiple Signaling Pathways in Cancer: The Rutin Therapeutic Approach. Cancers, 12.","DOI":"10.3390\/cancers12082276"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/s41392-025-02167-1","article-title":"Cancer chemoprevention: Signaling pathways and strategic approaches","volume":"10","author":"Ren","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Victoir, B., Croix, C., Gouilleux, F., and Pri\u00e9, G. (2024). Targeted Therapeutic Strategies for the Treatment of Cancer. Cancers, 16.","DOI":"10.3390\/cancers16020461"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"106356","DOI":"10.1016\/j.bioorg.2023.106356","article-title":"Design, synthesis and biological evaluation of novel 9-methyl-9H-purine and thieno[3, 2-d]pyrimidine derivatives as potent mTOR inhibitors","volume":"132","author":"Yang","year":"2023","journal-title":"Bioorg. Chem."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"104197","DOI":"10.1016\/j.bioorg.2020.104197","article-title":"Design, synthesis and biological evaluation of thieno[3,2-d]pyrimidine derivatives containing aroyl hydrazone or aryl hydrazide moieties for PI3K and mTOR dual inhibition","volume":"104","author":"Han","year":"2020","journal-title":"Bioorg. Chem."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1111\/cbdd.13425","article-title":"Design, synthesis, and biological evaluation of thieno[3,2-d]pyrimidine derivatives as potential simplified phosphatidylinositol 3-kinase alpha inhibitors","volume":"94","author":"Yang","year":"2019","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.ejmech.2014.10.022","article-title":"Design, synthesis and biological evaluation of novel thieno[3,2-d]pyrimidine derivatives possessing diaryl semicarbazone scaffolds as potent antitumor agents","volume":"87","author":"Liu","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"4023","DOI":"10.1021\/acs.jmedchem.7b00357","article-title":"Design, Synthesis, and Biological Evaluation of Dimorpholine Substituted Thienopyrimidines as Potential Class I PI3K\/mTOR Dual Inhibitors","volume":"60","author":"Zhan","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"5522","DOI":"10.1021\/jm800295d","article-title":"The Identification of 2-(1H-Indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a Potent, Selective, Orally Bioavailable Inhibitor of Class I PI3 Kinase for the Treatment of Cancer","volume":"51","author":"Folkes","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1021\/jm901284w","article-title":"Discovery of (Thienopyrimidin-2-yl)aminopyrimidines as Potent, Selective, and Orally Available Pan-PI3-Kinase and Dual Pan-PI3-Kinase\/mTOR Inhibitors for the Treatment of Cancer","volume":"53","author":"Sutherlin","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"7579","DOI":"10.1021\/jm2009327","article-title":"Discovery of a Potent, Selective, and Orally Available Class I Phosphatidylinositol 3-Kinase (PI3K)\/Mammalian Target of Rapamycin (mTOR) Kinase Inhibitor (GDC-0980) for the Treatment of Cancer","volume":"54","author":"Sutherlin","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"113963","DOI":"10.1016\/j.ejmech.2021.113963","article-title":"Dual target inhibitors based on EGFR: Promising anticancer agents for the treatment of cancers (2017-)","volume":"227","author":"Hu","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Jain, V., Bage, S., Dhiman, N., Singh, S., Yadav, A., Br\u00fcnnert, D., Sawant, D.M., and Goyal, P. (2026). Relevance of EGFR-HER2 Dual Inhibition in Breast Cancer. Targets, 4.","DOI":"10.3390\/targets4010010"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.bmcl.2008.12.011","article-title":"Thienopyrimidine-based dual EGFR\/ErbB-2 inhibitors","volume":"19","author":"Rheault","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.bmcl.2008.11.023","article-title":"Synthesis and stereochemical effects of pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines as EGFR and ErbB-2 inhibitors","volume":"19","author":"Stevens","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"118191","DOI":"10.1016\/j.ejmech.2025.118191","article-title":"Tubulin-based dual-target compounds and protein degraders for cancer therapy\u2014An updated review (2021-present)","volume":"301","author":"Li","year":"2026","journal-title":"Eur. J. Med. Chem."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"145923","DOI":"10.1016\/j.molstruc.2026.145923","article-title":"EGFR\/tubulin dual-targeting podophyllotoxin triazole ester derivatives: Design, synthesis, and anti-NSCLC activity evaluation","volume":"1364","author":"Lin","year":"2026","journal-title":"J. Mol. Struct."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1021\/acs.jmedchem.8b01391","article-title":"Design, Synthesis, and Biological Evaluation of 6-Substituted Thieno[3,2-d]pyrimidine Analogues as Dual Epidermal Growth Factor Receptor Kinase and Microtubule Inhibitors","volume":"62","author":"Romagnoli","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1186\/s12964-023-01400-0","article-title":"Dual blockade of EGFR and PI3K signaling pathways offers a therapeutic strategy for glioblastoma","volume":"21","author":"Guo","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"107714","DOI":"10.1016\/j.bioorg.2024.107714","article-title":"Design, synthesis and bioevaluation of dual EGFR-PI3K\u03b1 inhibitors for potential treatment of NSCLC","volume":"151","author":"Wang","year":"2024","journal-title":"Bioorg. Chem."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"3260","DOI":"10.1021\/acs.jmedchem.4c02478","article-title":"Design, Synthesis, and Biological Evaluation of Thieno[3,2-d]pyrimidine Derivatives as the First Bifunctional PI3K\u03b4 Isoform Selective\/Bromodomain and Extra-Terminal Inhibitors","volume":"68","author":"Ran","year":"2025","journal-title":"J. Med. Chem."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"113357","DOI":"10.1016\/j.ejmech.2021.113357","article-title":"Discovery of novel and potent PARP\/PI3K dual inhibitors for the treatment of cancer","volume":"217","author":"Wu","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1021\/acsmedchemlett.1c00412","article-title":"Macrocyclization as a Source of Desired Polypharmacology. Discovery of Triple PI3K\/mTOR\/PIM Inhibitors","volume":"12","author":"Alvarez","year":"2021","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"112024","DOI":"10.1016\/j.ejmech.2019.112024","article-title":"Design, synthesis, biological evaluation and molecular docking study of novel thieno[3,2-d]pyrimidine derivatives as potent FAK inhibitors","volume":"188","author":"Wang","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"14626","DOI":"10.1021\/acs.jmedchem.0c01174","article-title":"A Chemical Probe for Dark Kinase STK17B Derives Its Potency and High Selectivity through a Unique P-Loop Conformation","volume":"63","author":"Picado","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"113265","DOI":"10.1016\/j.ejmech.2021.113265","article-title":"Discovery of pyrazolo-thieno[3,2-d]pyrimidinylamino-phenyl acetamides as type-II pan-tropomyosin receptor kinase (TRK) inhibitors: Design, synthesis, and biological evaluation","volume":"216","author":"Yan","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"116689","DOI":"10.1016\/j.ejmech.2024.116689","article-title":"Design, synthesis and biological evaluation of novel SIRT3 inhibitors targeting both NAD+ and substrate binding sites for the treatment of acute myeloid leukemia","volume":"276","author":"Yang","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"3658","DOI":"10.1016\/j.bmc.2017.04.044","article-title":"2-Aminomethylthieno[3,2-d]pyrimidin-4(3H)-ones bearing 3-methylpyrazole hinge binding moiety: Highly potent, selective, and time-dependent inhibitors of Cdc7 kinase","volume":"25","author":"Kurasawa","year":"2017","journal-title":"Biorg. Med. Chem."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"8244","DOI":"10.1021\/acs.jmedchem.4c02978","article-title":"Development of Novel PRMT7 Inhibitors for the Treatment of Prostate Cancer","volume":"68","author":"Li","year":"2025","journal-title":"J. Med. Chem."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"26060","DOI":"10.1039\/C7RA04261B","article-title":"Discovery of new BTK inhibitors with B cell suppression activity bearing a 4,6-substituted thieno[3,2-d]pyrimidine scaffold","volume":"7","author":"Zhang","year":"2017","journal-title":"RSC Adv."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"11934","DOI":"10.1021\/acs.jmedchem.1c00459","article-title":"Identification of Thieno[3,2-d]pyrimidine Derivatives as Dual Inhibitors of Focal Adhesion Kinase and FMS-like Tyrosine Kinase 3","volume":"64","author":"Cho","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"107929","DOI":"10.1016\/j.bioorg.2024.107929","article-title":"Discovery and optimization of novel 4-morpholinothieno[3,2-d]pyrimidine derivatives as potent BET inhibitors for cancer therapy","volume":"153","author":"Ran","year":"2024","journal-title":"Bioorg. Chem."},{"key":"ref_217","doi-asserted-by":"crossref","unstructured":"Sirakanyan, S.N., Spinelli, D., Geronikaki, A., Hakobyan, E.K., Sahakyan, H., Arabyan, E., Zakaryan, H., Nersesyan, L.E., Aharonyan, A.S., and Danielyan, I.S. (2019). Synthesis, Antitumor Activity, and Docking Analysis of New Pyrido[3\u2032,2\u2032:4,5]furo(thieno)[3,2-d]pyrimidin-8-amines. Molecules, 24.","DOI":"10.3390\/molecules24213952"},{"key":"ref_218","doi-asserted-by":"crossref","unstructured":"Ruzi, Z., Buronov, A., Nie, L., Nasrullaev, A., Murtazaeva, Z., Kuryazov, R., Zhao, J., Efferth, T., Aisa, H.A., and Bozorov, K. (2025). Scaffold-Hopping Design and Synthesis of Thieno[3,2-d]pyrimidines: Anticancer Activity, Apoptosis Induction, and In Silico Inhibition of CDKs. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26178528"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7457\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T04:11:57Z","timestamp":1787631117000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7457"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":218,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167457"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167457","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]}}}