A Phase 1b/2 Dose-Escalation and Cohort-Expansion Study of the Noncovalent, Reversible Bruton's Tyrosine Kinase Inhibitor, SNS-062, in Patients With B-Lymphoid Malignancies

This is an open-label Phase 1b/2 study in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)or non hodgkin's lymphoma (NHL) who have failed prior standard of care therapies including a BTK inhibitor where one is approved for the indication.

开始日期2017-04-28

申办/合作机构

Sunesis Pharmaceuticals, Inc.

100 项与 ITK x BTK C481S 相关的临床结果

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100 项与 ITK x BTK C481S 相关的转化医学

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0 项与 ITK x BTK C481S 相关的专利（医药）

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项与 ITK x BTK C481S 相关的文献（医药）

2022-02-10·Blood

Overcoming resistance hurdles

Communications

作者: Thijssen, Rachel

Clin. outcomes in chronic lymphocytic leukemia (CLL) have greatly improved over the last 2 decades with the development of regimens combining cytotoxic drugs with anti-CD20 monoclonal antibodies, but outcomes vary significantly.In this article authors characterize a novel Bruton tyrosine kinase (BTK) inhibitor, vecabrutinib, that targets mutant BTK C481S and wild-type BTK in preclin. models.This is the first BTK inhibitor that also inhibits interleukin-2-inducible T-cell kinase (ITK) and can still bind to mutant BTK.

2018-09-06·Blood1区 · 医学

Noncovalent inhibition of C481S Bruton tyrosine kinase by GDC-0853: a new treatment strategy for ibrutinib-resistant CLL

1区 · 医学

Article

作者: Liu, Lichuan ; Cheney, Carolyn ; Young, Wendy B. ; Guinn, Daphne ; Fabian, Catherine A. ; Johnson, Amy J. ; Johnson, Adam R. ; Mantel, Rose ; Muhowski, Elizabeth M. ; Byrd, John C. ; Lehman, Amy ; Reiff, Sean D. ; Woyach, Jennifer A. ; Smith, Lisa

Key PointsInhibition of the ibrutinib-resistant C481S BTK mutant can be achieved by the reversible BTK inhibitor GDC-0853. BTK inhibitors, which lack ITK inhibition, preserve natural killer cell–mediated cellular cytotoxicity to CD20 directed monoclonal antibodies.

2018-07-01·Cell Research

PROTAC-induced BTK degradation as a novel therapy for mutated BTK C481S induced ibrutinib-resistant B-cell malignancies

Letter

作者: Zhao, Xingwang ; Rao, Yu ; Yang, Yiqing ; Ding, Ning ; Gao, Hongying ; Wu, Yue ; Song, Yuqin ; Hwang, Jinseok ; Zhao, Meng ; Sun, Yonghui ; Liu, Wanli

In this study, for the first time, we report the development of BTK-targeting degraders using the PROTAC strategy.These PROTACs could ef fi ciently degrade ibrutinib-sensitive BTK-WT (wild type).More importantly, our newly designed PROTACs also significantly induced the degradation of ibrutinib resistant BTK-C481S (50% degradation efficiency at 30 nM).Furthermore, our PROTAC mols. ef fi ciently inhibited cell proliferation and colony formation, while exhibited no obvious inhibition (>1000 nM) of ITK, EGFR, and TEC, which are major off-targets of ibrutinib.These data demonstrate the strong potential for developing PROTAC-based therapeutic mols.The results indicate that the PROTAC strategy (protein degradation instead of inhibition) could be adopted as a general and powerful therapeutic treatment for drug-resistant cancers in the future.