{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T17:01:33Z","timestamp":1750525293426},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Life Sciences"],"published-print":{"date-parts":[[2024,6]]},"DOI":"10.1016\/j.lfs.2024.122662","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T06:11:54Z","timestamp":1713939114000},"page":"122662","update-policy":"http:\/\/dx.doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"title":["TYM-3-98, a novel selective inhibitor of PI3K\u03b4, demonstrates promising preclinical antitumor activity in B-cell lymphomas"],"prefix":"10.1016","volume":"347","author":[{"given":"Si-yue","family":"Lou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan-li","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-mei","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-nan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai","family":"An","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"En-jun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun-liang","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua-jun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"8","key":"10.1016\/j.lfs.2024.122662_bb0005","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrc3774","article-title":"The tumour microenvironment in B cell lymphomas","volume":"14","author":"Scott","year":"2014","journal-title":"Nat. Rev. Cancer"},{"issue":"1","key":"10.1016\/j.lfs.2024.122662_bb0010","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41375-022-01764-1","article-title":"A comparison of the international consensus and 5th World Health Organization classifications of mature B-cell lymphomas","volume":"37","author":"Falini","year":"2023","journal-title":"Leukemia"},{"issue":"7","key":"10.1016\/j.lfs.2024.122662_bb0015","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1007\/s13238-020-00694-x","article-title":"HDAC inhibitors overcome immunotherapy resistance in B-cell lymphoma","volume":"11","author":"Wang","year":"2020","journal-title":"Protein Cell"},{"issue":"1","key":"10.1016\/j.lfs.2024.122662_bb0020","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s13045-021-01134-x","article-title":"Targeting the tumor microenvironment in B-cell lymphoma: challenges and opportunities","volume":"14","author":"Liu","year":"2021","journal-title":"J. Hematol. Oncol."},{"issue":"2","key":"10.1016\/j.lfs.2024.122662_bb0025","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/nrd4204","article-title":"PI3K and cancer: lessons, challenges and opportunities","volume":"13","author":"Fruman","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"issue":"5573","key":"10.1016\/j.lfs.2024.122662_bb0030","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1126\/science.296.5573.1655","article-title":"The phosphoinositide 3-kinase pathway","volume":"296","author":"Cantley","year":"2002","journal-title":"Science (New York, N.Y.)"},{"issue":"7","key":"10.1016\/j.lfs.2024.122662_bb0035","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1158\/2159-8290.CD-11-0249","article-title":"PI3K\u03b4 inhibitors in cancer: rationale and serendipity merge in the clinic","volume":"1","author":"Fruman","year":"2011","journal-title":"Cancer Discov."},{"issue":"4","key":"10.1016\/j.lfs.2024.122662_bb0040","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.cellsig.2010.10.002","article-title":"Phosphoinositide 3-kinase delta (PI3K\u03b4) in leukocyte signaling and function","volume":"23","author":"Fung-Leung","year":"2011","journal-title":"Cell. Signal."},{"issue":"3","key":"10.1016\/j.lfs.2024.122662_bb0045","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1182\/blood-2016-02-702761","article-title":"Idelalisib in the management of lymphoma","volume":"128","author":"Cheah","year":"2016","journal-title":"Blood"},{"issue":"4","key":"10.1016\/j.lfs.2024.122662_bb0050","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1002\/med.21341","article-title":"Targeting PI3K\u03b4: emerging therapy for chronic lymphocytic leukemia and beyond","volume":"35","author":"Wei","year":"2015","journal-title":"Med. Res. Rev."},{"issue":"8","key":"10.1016\/j.lfs.2024.122662_bb0055","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1158\/1078-0432.CCR-22-2939","article-title":"The oral PI3K\u03b4 inhibitor Linperlisib for the treatment of relapsed and\/or refractory follicular lymphoma: a phase II, single-arm, open-label clinical trial","volume":"29","author":"Wang","year":"2023","journal-title":"Clinical cancer research\u202f: an official journal of the American Association for Cancer Research."},{"issue":"2","key":"10.1016\/j.lfs.2024.122662_bb0060","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20020412","article-title":"Targeting PI3K signaling in acute lymphoblastic leukemia","volume":"20","author":"Sanchez","year":"2019","journal-title":"Int. J. Mol. Sci."},{"issue":"7","key":"10.1016\/j.lfs.2024.122662_bb0065","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1158\/1078-0432.CCR-14-2034","article-title":"Idelalisib: first-in-class PI3K Delta inhibitor for the treatment of chronic lymphocytic leukemia, small lymphocytic leukemia, and follicular lymphoma","volume":"21","author":"Yang","year":"2015","journal-title":"Clinical cancer research\u202f: an official journal of the American Association for Cancer Research."},{"issue":"2","key":"10.1016\/j.lfs.2024.122662_bb0070","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s40264-018-0778-4","article-title":"Safety and tolerability of Phosphatidylinositol-3-kinase (PI3K) inhibitors in oncology","volume":"42","author":"Curigliano","year":"2019","journal-title":"Drug Saf."},{"issue":"16","key":"10.1016\/j.lfs.2024.122662_bb0075","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1182\/blood-2018-08-867499","article-title":"Parsaclisib, a potent and highly selective PI3K\u03b4 inhibitor, in patients with relapsed or refractory B-cell malignancies","volume":"133","author":"Forero-Torres","year":"2019","journal-title":"Blood"},{"issue":"1","key":"10.1016\/j.lfs.2024.122662_bb0080","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1124\/jpet.120.265538","article-title":"Parsaclisib is a next-generation phosphoinositide 3-kinase \u03b4 inhibitor with reduced hepatotoxicity and potent antitumor and immunomodulatory activities in models of B-cell malignancy","volume":"374","author":"Shin","year":"2020","journal-title":"J. Pharmacol. Exp. Ther."},{"issue":"5","key":"10.1016\/j.lfs.2024.122662_bb0085","doi-asserted-by":"crossref","first-page":"3849","DOI":"10.1021\/acs.jmedchem.1c01520","article-title":"Discovery of novel Indazoles as potent and selective PI3K\u03b4 inhibitors with high efficacy for treatment of hepatocellular carcinoma","volume":"65","author":"Qi","year":"2022","journal-title":"J. Med. Chem."},{"issue":"196","key":"10.1016\/j.lfs.2024.122662_bb0090","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3005747","article-title":"mTORC1 inhibition is required for sensitivity to PI3K p110\u03b1 inhibitors in PIK3CA-mutant breast cancer","volume":"5","author":"Elkabets","year":"2013","journal-title":"Sci. Transl. Med."},{"issue":"1","key":"10.1016\/j.lfs.2024.122662_bb0095","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1124\/jpet.117.244947","article-title":"INCB040093 is a novel PI3K\u03b4 inhibitor for the treatment of B cell lymphoid malignancies","volume":"364","author":"Shin","year":"2018","journal-title":"J. Pharmacol. Exp. Ther."},{"issue":"7","key":"10.1016\/j.lfs.2024.122662_bb0100","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1111\/cas.13263","article-title":"Puquitinib, a novel orally available PI3K\u03b4 inhibitor, exhibits potent antitumor efficacy against acute myeloid leukemia","volume":"108","author":"Xie","year":"2017","journal-title":"Cancer Sci."},{"issue":"1","key":"10.1016\/j.lfs.2024.122662_bb0105","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41401-021-00644-1","article-title":"SAF-248, a novel PI3K\u03b4-selective inhibitor, potently suppresses the growth of diffuse large B-cell lymphoma","volume":"43","author":"Zhang","year":"2022","journal-title":"Acta Pharmacol. Sin."},{"issue":"10","key":"10.1016\/j.lfs.2024.122662_bb0110","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/j.leukres.2013.07.028","article-title":"Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma and its attenuation by Ibrutinib induces apoptosis","volume":"37","author":"Cinar","year":"2013","journal-title":"Leuk. Res."},{"issue":"30","key":"10.1016\/j.lfs.2024.122662_bb0115","doi-asserted-by":"crossref","first-page":"12420","DOI":"10.1073\/pnas.1305656110","article-title":"PTEN loss defines a PI3K\/AKT pathway-dependent germinal center subtype of diffuse large B-cell lymphoma","volume":"110","author":"Pfeifer","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"2","key":"10.1016\/j.lfs.2024.122662_bb0120","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1182\/blood-2010-03-275305","article-title":"CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability","volume":"117","author":"Lannutti","year":"2011","journal-title":"Blood"},{"issue":"14","key":"10.1016\/j.lfs.2024.122662_bb0125","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1007\/s40265-014-0285-6","article-title":"Idelalisib: first global approval","volume":"74","author":"Markham","year":"2014","journal-title":"Drugs"},{"issue":"2","key":"10.1016\/j.lfs.2024.122662_bb0130","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1182\/blood-2016-03-707133","article-title":"Idelalisib given front-line for treatment of chronic lymphocytic leukemia causes frequent immune-mediated hepatotoxicity","volume":"128","author":"Lampson","year":"2016","journal-title":"Blood"},{"key":"10.1016\/j.lfs.2024.122662_bb0135","series-title":"ZYDELIG (idelalisib) US prescribing Information","author":"Inc. GS","year":"2014"},{"issue":"7","key":"10.1016\/j.lfs.2024.122662_bb0140","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/nrc839","article-title":"The phosphatidylinositol 3-kinase AKT pathway in human cancer","volume":"2","author":"Vivanco","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.lfs.2024.122662_bb0145","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.semcancer.2019.07.009","article-title":"PI3K\/Akt\/mTOR inhibitors in cancer: at the bench and bedside","volume":"59","author":"Alzahrani","year":"2019","journal-title":"Semin. Cancer Biol."},{"issue":"10","key":"10.1016\/j.lfs.2024.122662_bb0150","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1093\/annonc\/mdw282","article-title":"First-in-human phase I study of copanlisib (BAY 80-6946), an intravenous pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors and non-Hodgkin\u2019s lymphomas","volume":"27","author":"Patnaik","year":"2016","journal-title":"Annals of oncology\u202f: official journal of the European Society for Medical Oncology."},{"issue":"12","key":"10.1016\/j.lfs.2024.122662_bb0155","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1038\/nrc1753","article-title":"Oncogenic PI3K deregulates transcription and translation","volume":"5","author":"Bader","year":"2005","journal-title":"Nat. Rev. Cancer"},{"issue":"13","key":"10.1016\/j.lfs.2024.122662_bb0160","doi-asserted-by":"crossref","first-page":"3603","DOI":"10.1182\/blood-2011-05-352492","article-title":"The phosphoinositide 3\u2032-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia","volume":"118","author":"Hoellenriegel","year":"2011","journal-title":"Blood"},{"issue":"12","key":"10.1016\/j.lfs.2024.122662_bb0165","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0083830","article-title":"The PI3-kinase delta inhibitor idelalisib (GS-1101) targets integrin-mediated adhesion of chronic lymphocytic leukemia (CLL) cell to endothelial and marrow stromal cells","volume":"8","author":"Fiorcari","year":"2013","journal-title":"PLoS One"},{"issue":"11","key":"10.1016\/j.lfs.2024.122662_bb0170","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1056\/NEJMoa1314583","article-title":"PI3K\u03b4 inhibition by idelalisib in patients with relapsed indolent lymphoma","volume":"370","author":"Gopal","year":"2014","journal-title":"N. Engl. J. Med."},{"issue":"7360","key":"10.1016\/j.lfs.2024.122662_bb0175","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nature10351","article-title":"Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma","volume":"476","author":"Morin","year":"2011","journal-title":"Nature"},{"issue":"11","key":"10.1016\/j.lfs.2024.122662_bb0180","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1080\/15592294.2019.1633867","article-title":"EZH2 upregulates the PI3K\/AKT pathway through IGF1R and MYC in clinically aggressive chronic lymphocytic leukaemia","volume":"14","author":"Kosalai","year":"2019","journal-title":"Epigenetics"},{"issue":"11","key":"10.1016\/j.lfs.2024.122662_bb0185","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1056\/NEJMoa1315226","article-title":"Idelalisib and rituximab in relapsed chronic lymphocytic leukemia","volume":"370","author":"Furman","year":"2014","journal-title":"N. Engl. J. Med."},{"issue":"25","key":"10.1016\/j.lfs.2024.122662_bb0190","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1182\/blood-2015-03-630947","article-title":"A phase 2 study of idelalisib plus rituximab in treatment-na\u00efve older patients with chronic lymphocytic leukemia","volume":"126","author":"O\u2019Brien","year":"2015","journal-title":"Blood"},{"issue":"3","key":"10.1016\/j.lfs.2024.122662_bb0195","doi-asserted-by":"crossref","first-page":"690","DOI":"10.3324\/haematol.2020.274258","article-title":"Subtype-specific and co-occurring genetic alterations in B-cell non-Hodgkin lymphoma","volume":"107","author":"Ma","year":"2022","journal-title":"Haematologica"},{"issue":"10","key":"10.1016\/j.lfs.2024.122662_bb0200","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s12325-017-0612-x","article-title":"Rituximab in B-cell hematologic malignancies: a review of 20 years of clinical experience","volume":"34","author":"Salles","year":"2017","journal-title":"Adv. Ther."},{"issue":"9","key":"10.1016\/j.lfs.2024.122662_bb0205","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1080\/14740338.2020.1802424","article-title":"Safety considerations with targeted therapy drugs for B-cell non-Hodgkin lymphoma","volume":"19","author":"Makita","year":"2020","journal-title":"Expert Opin. Drug Saf."},{"issue":"10","key":"10.1016\/j.lfs.2024.122662_bb0210","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/s41573-021-00209-1","article-title":"PI3K inhibitors are finally coming of age","volume":"20","author":"Vanhaesebroeck","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"issue":"5","key":"10.1016\/j.lfs.2024.122662_bb0215","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1001\/jamainternmed.2023.0190","article-title":"Clinical trials portfolio and regulatory history of Idelalisib in indolent non-Hodgkin lymphoma: a systematic review and Meta-analysis","volume":"183","author":"Banerjee","year":"2023","journal-title":"JAMA Intern. Med."},{"issue":"1","key":"10.1016\/j.lfs.2024.122662_bb0220","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3324\/haematol.2022.281266","article-title":"PI3K inhibitors in chronic lymphocytic leukemia: where do we go from here?","volume":"108","author":"Sk\u00e5nland","year":"2023","journal-title":"Haematologica"},{"issue":"1","key":"10.1016\/j.lfs.2024.122662_bb0225","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.1016\/S2352-3026(18)30196-0","article-title":"Umbralisib in combination with ibrutinib in patients with relapsed or refractory chronic lymphocytic leukaemia or mantle cell lymphoma: a multicentre phase 1-1b study","volume":"6","author":"Davids","year":"2019","journal-title":"The Lancet Haematology."}],"container-title":["Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0024320524002522?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0024320524002522?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T07:44:21Z","timestamp":1715240661000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0024320524002522"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6]]},"references-count":45,"alternative-id":["S0024320524002522"],"URL":"https:\/\/doi.org\/10.1016\/j.lfs.2024.122662","relation":{},"ISSN":["0024-3205"],"issn-type":[{"value":"0024-3205","type":"print"}],"subject":[],"published":{"date-parts":[[2024,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"TYM-3-98, a novel selective inhibitor of PI3K\u03b4, demonstrates promising preclinical antitumor activity in B-cell lymphomas","name":"articletitle","label":"Article Title"},{"value":"Life Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.lfs.2024.122662","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"122662"}}