Discovery of a highly potent and selective Bruton’s tyrosine kinase inhibitor avoiding impairment of ADCC effects for B-cell non-Hodgkin lymphoma
作者机构：Anhui Province Key Laboratory of Medical Physics and TechnologyInstitute of Health and Medical TechnologyHefei Institutes of Physical ScienceChinese Academy of Sciences230031 HefeiAnhuiP.R.China University of Science and Technology of China230036 HefeiAnhuiP.R.China Hefei Cancer HospitalChinese Academy of Sciences230031 HefeiAnhuiP.R.China Precision Medicine Research Laboratory of Anhui Province230088 HefeiAnhuiP.R.China Precision Targeted Therapy Discovery CenterInstitute of Technology InnovationHefei Institutes of Physical ScienceChinese Academy of Sciences230088 HefeiAnhuiP.R.China Institutes of Physical Science and Information TechnologyAnhui University230601 HefeiAnhuiP.R.China
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2020年第5卷第1期
页 面：814-816页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：supported by the National Natural Science Foundation of China(Grant Nos.81773777,81872748,and 81803366) the National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”of China(Grant No.2018ZX09711002) the Natural Science Foundation of Anhui Province(Grant No.1808085MH268) the China Postdoctoral Science Foundation(Grants Nos.2018T110634 and 2018M630720) the Frontier Science Key Research Program of CAS(Grant No.QYZDB-SSW-SLH037) the Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology(Grant No.2019HSCCIP011)the CASHIPS Director’s Fund(Grant No.BJPY2019A03) the Key Program of 13th five-year plan of CASHIPS(Grant No.KP-2017-26)
主 题：lymphoma ADCC lymphocytic
摘 要：Dear Editor,Bruton’s tyrosine kinase(BTK)plays a crucial role in the B-cell receptor(BCR)signaling which is essential for B-cell proliferation,differentiation,and cell *** BCR activation has been identified as a major pathogenic factor in several B-cell non-Hodgkin lymphoma(B-NHL)subtypes,including diffuse large Bcell lymphoma(DLBCL),mantle cell lymphoma(MCL),follicular lymphoma(FL),and chronic lymphocytic leukemia(CLL).1 Therefore,BTK has been recognized as a validated therapeutic target for B-cell ***,the first approved BTK inhibitor that binds irreversibly to cysteine residue 481,has shown potent clinical activity in the majority of CD20 positive B-cell malignancies.2 However,due to the inhibition of off-target kinases such as EGFR,ITK,and TXK,which have a cysteine residue at the identical position of Cys481 of BTK,Ibrutinib also results in some adverse events,such as the antagonizing Rituximab-dependent NK-cell-mediated antibody-dependent cell-mediated cytotoxicity(ADCC)due to its irreversible binding to ITK,which is required for FcR-stimulated NK cell function.3 Although several secondary generation inhibitors have shown improved selectivity,4,5 more pharmacologically diverse novel inhibitors are still highly demanded in the clinic.
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