{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:59:43Z","timestamp":1791392383418,"version":"4.3.3"},"reference-count":67,"publisher":"Royal Society of Chemistry (RSC)","issue":"44","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":258,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100009169","name":"Assiut University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009169","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rsc.org"],"crossmark-restriction":true},"short-container-title":["RSC Adv."],"abstract":"<jats:p>Simultaneous inhibition of CDK2 and TRKA presents a promising therapeutic avenue for cancer treatment, capitalizing on the critical roles of CDK2 in cell cycle regulation and TRKA in tumor cell survival and progression.<\/jats:p>","DOI":"10.1039\/d6ra02521h","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:21:38Z","timestamp":1789554098000},"page":"55449-55469","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual inhibitors of CDK2 and TRKA kinases: design, synthesis, antiproliferative activity and molecular modeling of novel pyrazolopyrimidine derivatives"],"prefix":"10.1039","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0888-1605","authenticated-orcid":false,"given":"Mohamed H.","family":"Attia","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, October 6 University, 6 of October City, Giza, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7698-9757","authenticated-orcid":false,"given":"Deena S.","family":"Lasheen","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abbassia 11566, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nermin","family":"Samir","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abbassia 11566, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azza T.","family":"Taher","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt"},{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, October 6 University (O6U), Giza, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatem A.","family":"Abdel-Aziz","sequence":"additional","affiliation":[{"name":"Department of Applied Organic Chemistry, National Research Center, Dokki, Cairo 12622, Egypt"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria, Canal El Mahmoudia St., Alexandria 21648, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalal A.","family":"Abou El Ella","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abbassia 11566, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"292","published-online":{"date-parts":[[2026]]},"reference":[{"key":"D6RA02521H\/cit1\/1","doi-asserted-by":"publisher","first-page":"5489","DOI":"10.3390\/ijms25105489","volume":"25","author":"Li","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"D6RA02521H\/cit2\/1","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1038\/s41417-021-00408-3","volume":"29","author":"Vella","year":"2022","journal-title":"Cancer Gene Ther."},{"key":"D6RA02521H\/cit3\/1","doi-asserted-by":"publisher","first-page":"112025","DOI":"10.1016\/j.ejmech.2019.112025","volume":"188","author":"Sun","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"D6RA02521H\/cit4\/1","doi-asserted-by":"publisher","first-page":"108899","DOI":"10.1016\/j.bioorg.2025.108899","author":"Eldeeb","year":"2025","journal-title":"Bioorg. Chem."},{"key":"D6RA02521H\/cit5\/1","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/nrc2602","volume":"9","author":"Malumbres","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"D6RA02521H\/cit6\/1","doi-asserted-by":"publisher","first-page":"136692","DOI":"10.1016\/j.molstruc.2023.136692","volume":"1295","author":"Al-Hussain","year":"2024","journal-title":"J. Mol. Struct."},{"key":"D6RA02521H\/cit7\/1","doi-asserted-by":"publisher","first-page":"13429","DOI":"10.1038\/s41598-017-12868-5","volume":"7","author":"Ba\u010devi\u0107","year":"2017","journal-title":"Sci. Rep."},{"key":"D6RA02521H\/cit8\/1","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1038\/nrc.2016.138","volume":"17","author":"Otto","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"D6RA02521H\/cit9\/1","doi-asserted-by":"publisher","first-page":"14865","DOI":"10.1039\/D2RA01968J","volume":"12","author":"Nassar","year":"2022","journal-title":"RSC Adv."},{"key":"D6RA02521H\/cit10\/1","doi-asserted-by":"publisher","first-page":"2628","DOI":"10.1016\/j.cell.2023.05.013","volume":"186","author":"Arora","year":"2023","journal-title":"Cell"},{"key":"D6RA02521H\/cit11\/1","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1021\/ml100051d","volume":"1","author":"Paruch","year":"2010","journal-title":"ACS Med. Chem. Lett."},{"key":"D6RA02521H\/cit12\/1","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/S0304-3835(01)00530-4","volume":"169","author":"Nakagawara","year":"2001","journal-title":"Cancer Lett."},{"key":"D6RA02521H\/cit13\/1","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1146\/annurev.biochem.72.121801.161629","volume":"72","author":"Huang","year":"2003","journal-title":"Annu. Rev. Biochem."},{"key":"D6RA02521H\/cit14\/1","doi-asserted-by":"publisher","first-page":"217023","DOI":"10.1016\/j.canlet.2024.217023","volume":"597","author":"Regua","year":"2024","journal-title":"Cancer Lett."},{"key":"D6RA02521H\/cit15\/1","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1158\/2159-8290.CD-14-0765","volume":"5","author":"Vaishnavi","year":"2015","journal-title":"Cancer Discovery"},{"key":"D6RA02521H\/cit16\/1","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/s41571-018-0113-0","volume":"15","author":"Cocco","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"D6RA02521H\/cit17\/1","doi-asserted-by":"publisher","DOI":"10.1186\/s13065-024-01166-7","volume":"18","author":"Metwally","year":"2024","journal-title":"BMC Chem."},{"key":"D6RA02521H\/cit18\/1","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1158\/2159-8290.CD-18-0484","volume":"8","author":"Drilon","year":"2018","journal-title":"Cancer Discovery"},{"key":"D6RA02521H\/cit19\/1","doi-asserted-by":"publisher","first-page":"127712","DOI":"10.1016\/j.bmcl.2020.127712","volume":"31","author":"Zhang","year":"2021","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"D6RA02521H\/cit20\/1","doi-asserted-by":"publisher","first-page":"105431","DOI":"10.1016\/j.bioorg.2021.105431","volume":"117","author":"Almehmadi","year":"2021","journal-title":"Bioorg. Chem."},{"key":"D6RA02521H\/cit21\/1","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1002\/cmdc.200600302","volume":"2","author":"Brasca","year":"2007","journal-title":"ChemMedChem"},{"key":"D6RA02521H\/cit22\/1","doi-asserted-by":"publisher","first-page":"35226","DOI":"10.18632\/oncotarget.26215","volume":"9","author":"Kim","year":"2018","journal-title":"Oncotarget"},{"key":"D6RA02521H\/cit23\/1","doi-asserted-by":"publisher","first-page":"2696","DOI":"10.3390\/molecules26092696","volume":"26","author":"Giraud","year":"2021","journal-title":"Molecules"},{"key":"D6RA02521H\/cit24\/1","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.3390\/ph17121667","volume":"17","author":"Attia","year":"2024","journal-title":"Pharmaceuticals"},{"key":"D6RA02521H\/cit25\/1","doi-asserted-by":"publisher","first-page":"3681","DOI":"10.1039\/B607442A","volume":"4","author":"Christoforou","year":"2006","journal-title":"Org. Biomol. Chem."},{"key":"D6RA02521H\/cit26\/1","doi-asserted-by":"publisher","first-page":"13024","DOI":"10.1016\/j.tet.2007.10.014","volume":"63","author":"Kantevari","year":"2007","journal-title":"Tetrahedron"},{"key":"D6RA02521H\/cit27\/1","doi-asserted-by":"publisher","first-page":"3024","DOI":"10.1016\/j.bmcl.2016.05.019","volume":"26","author":"Prajapti","year":"2016","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"D6RA02521H\/cit28\/1","doi-asserted-by":"publisher","first-page":"13645","DOI":"10.3390\/molecules181113645","volume":"18","author":"Dou","year":"2013","journal-title":"Molecules"},{"issue":"6","key":"D6RA02521H\/cit29\/1","doi-asserted-by":"publisher","first-page":"577","DOI":"10.2174\/157340608786242115","volume":"4","author":"Kumar","year":"2008","journal-title":"Med. Chem."},{"key":"D6RA02521H\/cit30\/1","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.polymertesting.2015.10.006","volume":"48","author":"Ortyl","year":"2015","journal-title":"Polym. Test."},{"key":"D6RA02521H\/cit31\/1","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1002\/cjoc.201500872","volume":"34","author":"Shen","year":"2016","journal-title":"Chin. J. Chem."},{"key":"D6RA02521H\/cit32\/1","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1039\/C4QO00358F","volume":"2","author":"Girard","year":"2015","journal-title":"Org. Chem. Front."},{"key":"D6RA02521H\/cit33\/1","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1515\/gps-2022-0009","volume":"11","author":"Moustafa","year":"2022","journal-title":"Green Process. Synth."},{"issue":"23","key":"D6RA02521H\/cit34\/1","doi-asserted-by":"publisher","first-page":"7155","DOI":"10.1016\/S0040-4020(01)86083-X","volume":"44","author":"Ried","year":"1988","journal-title":"Tetrahedron"},{"key":"D6RA02521H\/cit35\/1","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1007\/s11030-019-09976-x","volume":"24","author":"Alizadeh-Kouzehrash","year":"2020","journal-title":"Mol. Diversity"},{"key":"D6RA02521H\/cit36\/1","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/j.tranon.2016.08.007","volume":"9","author":"Wang","year":"2016","journal-title":"Transl. Oncol."},{"key":"D6RA02521H\/cit37\/1","doi-asserted-by":"publisher","first-page":"3244","DOI":"10.1158\/1078-0432.CCR-08-1815","volume":"15","author":"Brodeur","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"D6RA02521H\/cit38\/1","doi-asserted-by":"publisher","first-page":"27751","DOI":"10.1074\/jbc.M111.264903","volume":"286","author":"Dixon","year":"2011","journal-title":"J. Biol. Chem."},{"key":"D6RA02521H\/cit39\/1","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/s41571-018-0113-0","volume":"15","author":"Cocco","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"D6RA02521H\/cit40\/1","doi-asserted-by":"publisher","first-page":"2310","DOI":"10.1080\/10428190701665988","volume":"48","author":"Kujawski","year":"2007","journal-title":"Leuk. Lymphoma"},{"key":"D6RA02521H\/cit41\/1","doi-asserted-by":"publisher","first-page":"104615","DOI":"10.1016\/j.bioorg.2020.104615","volume":"108","author":"El-Naggar","year":"2021","journal-title":"Bioorg. Chem."},{"key":"D6RA02521H\/cit42\/1","doi-asserted-by":"publisher","first-page":"12483","DOI":"10.1093\/nar\/gkaa1002","volume":"48","author":"Hume","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"D6RA02521H\/cit43\/1","doi-asserted-by":"publisher","first-page":"6023","DOI":"10.3390\/cancers13236023","volume":"13","author":"Hassiepen","year":"2021","journal-title":"Cancers"},{"key":"D6RA02521H\/cit44\/1","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s12943-019-1029-8","volume":"18","author":"Gong","year":"2019","journal-title":"Mol. Cancer"},{"key":"D6RA02521H\/cit45\/1","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.semcancer.2019.08.020","volume":"66","author":"Das","year":"2020","journal-title":"Semin. Cancer Biol."},{"key":"D6RA02521H\/cit46\/1","doi-asserted-by":"publisher","first-page":"115960","DOI":"10.1016\/j.bmc.2020.115960","volume":"32","author":"Abolhasani","year":"2021","journal-title":"Bioorg. Med. Chem."},{"key":"D6RA02521H\/cit47\/1","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/s41419-024-06947-5","volume":"15","author":"Schuermans","year":"2024","journal-title":"Cell Death Dis."},{"key":"D6RA02521H\/cit48\/1","doi-asserted-by":"publisher","first-page":"2116","DOI":"10.1021\/acschembio.5b00398","volume":"10","author":"Alexander","year":"2015","journal-title":"ACS Chem. Biol."},{"key":"D6RA02521H\/cit49\/1","doi-asserted-by":"publisher","first-page":"4589","DOI":"10.3390\/molecules24244589","volume":"24","author":"Mohammad","year":"2019","journal-title":"Molecules"},{"key":"D6RA02521H\/cit50\/1","doi-asserted-by":"publisher","first-page":"2360","DOI":"10.1021\/cb4003283","volume":"8","author":"Martin","year":"2013","journal-title":"ACS Chem. Biol."},{"key":"D6RA02521H\/cit51\/1","doi-asserted-by":"publisher","first-page":"127712","DOI":"10.1016\/j.bmcl.2020.127712","volume":"31","author":"Zhang","year":"2021","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"D6RA02521H\/cit52\/1","doi-asserted-by":"publisher","first-page":"W257","DOI":"10.1093\/nar\/gky318","volume":"46","author":"Banerjee","year":"2018","journal-title":"Nucleic Acids Res."},{"issue":"5","key":"D6RA02521H\/cit53\/1","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1055\/s-0031-1296392","volume":"59","author":"Chhabria","year":"2011","journal-title":"Arzneimittelforschung"},{"key":"D6RA02521H\/cit54\/1","doi-asserted-by":"publisher","first-page":"10285","DOI":"10.1039\/c5ra27017k","volume":"6","author":"Chaube","year":"2016","journal-title":"RSC Adv."},{"key":"D6RA02521H\/cit55\/1","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1002\/ardp.201900383","author":"Istrefi","year":"2020","journal-title":"Arch. Pharm. (Weinheim, Ger.)"},{"issue":"2","key":"D6RA02521H\/cit56\/1","first-page":"123","volume":"12","author":"Manai","year":"2010","journal-title":"J. Soc. Chim. Tunis."},{"key":"D6RA02521H\/cit57\/1","author":"Bokri","unstructured":"K.Bokri ,  M. L.Efrit ,  A.Ben Akacha ,  An efficient two-step synthesis of novel substituted pyrazolo[1,5-a]-[1,3,5]-triazines and pyrazolo[1,5-a]-[1,3,5] triazinones ,  http:\/\/heteroletters.org"},{"key":"D6RA02521H\/cit58\/1","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.1080\/00397910701473317","volume":"37","author":"Elgemeie","year":"2007","journal-title":"Synth. Commun."},{"key":"D6RA02521H\/cit59\/1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bioorg.2019.01.008","volume":"86","author":"Ali","year":"2019","journal-title":"Bioorg. Chem."},{"key":"D6RA02521H\/cit60\/1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bioorg.2019.01.008","volume":"86","author":"Ali","year":"2019","journal-title":"Bioorg. Chem."},{"issue":"7","key":"D6RA02521H\/cit61\/1","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1016\/S0040-4020(01)85083-3","volume":"50","author":"SanMart\u00edn","year":"1994","journal-title":"Tetrahedron"},{"key":"D6RA02521H\/cit62\/1","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1038\/nrd4504","volume":"14","author":"Asghar","year":"2015","journal-title":"Nat. Rev. Drug Discovery"},{"key":"D6RA02521H\/cit63\/1","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/j.apsb.2020.05.004","volume":"11","author":"Jiang","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"D6RA02521H\/cit64\/1","doi-asserted-by":"publisher","first-page":"105","DOI":"10.3390\/cancers10040105","volume":"10","author":"Lange","year":"2018","journal-title":"Cancers"},{"key":"D6RA02521H\/cit65\/1","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"D6RA02521H\/cit66\/1","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/0022-1759(91)90198-O","volume":"139","author":"Nicoletti","year":"1991","journal-title":"J. Immunol. Methods"},{"key":"D6RA02521H\/cit67\/1","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/0022-1759(95)00072-I","volume":"184","author":"Vermes","year":"1995","journal-title":"J. Immunol. Methods"}],"container-title":["RSC Advances"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/pubs.rsc.org\/RA\/article-pdf\/doi\/10.1039\/D6RA02521H\/0\/D6RA02521H.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:39:13Z","timestamp":1791391153000},"score":1,"resource":{"primary":{"URL":"http:\/\/pubs.rsc.org\/RA\/article-lookup\/doi\/10.1039\/D6RA02521H"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":67,"journal-issue":{"issue":"44","published-print":{"date-parts":[[2026,10,7]]}},"URL":"https:\/\/doi.org\/10.1039\/d6ra02521h","relation":{"has-review":[{"id-type":"doi","id":"10.1039\/D6RA02521H\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1039\/D6RA02521H\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1039\/D6RA02521H\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1039\/D6RA02521H\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1039\/D6RA02521H\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1039\/D6RA02521H\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1039\/D6RA02521H\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1039\/D6RA02521H\/v2\/decision1","asserted-by":"object"}]},"ISSN":["2046-2069"],"issn-type":[{"value":"2046-2069","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026]]}}}