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An Assessment ofKinase Selectivity, Enzyme InhibitionKinetics and in Vitro Activity for Several Bruton Tyrosine Kinase(BTK) Inhibitors 几种布鲁顿酪氨酸激酶（BTK）抑制剂的激酶选择性、酶抑制动力学和体外活性评估

Figshare Pub Date : 2025-11-18 DOI: 10.1021/acsptsci.5c00412.s002

Ana Corrionero (2264263), Xiaohu Zhang (391063), Patricia Alfonso (2416153), Patrick J. Morris (1347459), Carleen Klumpp-Thomas (3371171), Christopher Melani (18850803), Crystal McKnight (3371156), James D. Phelan (18226892), David Holland (495482), Kelli Wilson (3090900), Scott B. Hoyt (1601755), Mark Roschewski (14983811), Peter J. Tonge (262325), Wyndham Wilson (7311569), Michele Ceribelli (90489), Louis M. Staudt (2384083), Craig J. Thomas (17880)

{"title":"An Assessment ofKinase Selectivity, Enzyme InhibitionKinetics and in Vitro Activity for Several Bruton Tyrosine Kinase(BTK) Inhibitors","authors":"Ana Corrionero (2264263), Xiaohu Zhang (391063), Patricia Alfonso (2416153), Patrick J. Morris (1347459), Carleen Klumpp-Thomas (3371171), Christopher Melani (18850803), Crystal McKnight (3371156), James D. Phelan (18226892), David Holland (495482), Kelli Wilson (3090900), Scott B. Hoyt (1601755), Mark Roschewski (14983811), Peter J. Tonge (262325), Wyndham Wilson (7311569), Michele Ceribelli (90489), Louis M. Staudt (2384083), Craig J. Thomas (17880)","doi":"10.1021/acsptsci.5c00412.s002","DOIUrl":"https://doi.org/10.1021/acsptsci.5c00412.s002","url":null,"abstract":"Inhibitors of the Bruton’s tyrosine kinase (BTK) are of broad utility in the treatment of multiple diseases including several B-cell malignancies via effective blockade of oncogenic B-cell receptor (BCR) signaling. BTK is a cytoplasmic tyrosine kinase which harbors a targetable cysteine residue (Cys481) and the majority of BTK inhibitors are covalent modifiers directed at this position. Despite possessing a common mechanism of action, BTK inhibitors differ in key attributes including off-target kinome profiles, tolerability, pharmacokinetics and the underlying BTK inhibition kinetics. These characteristics play a significant role in the ultimate utility of these drugs. Herein, we compare several clinically active BTK inhibitors in biochemical and in vitro assays to gain a broader appreciation of the similarities and differences that govern the success of this important drug class. The combined datasets highlight that each agent has excellent on-target potency and good BTK selectivity. The data further suggests an association between optimized BTK inhibition kinetics and in vitro cytotoxicity profiles.","PeriodicalId":523708,"journal":{"name":"Figshare","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147920599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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