2. Academic Validation
  3. Discovery of novel pyrazole derivatives as potential anticancer agents in MCL

Discovery of novel pyrazole derivatives as potential anticancer agents in MCL

  • Bioorg Med Chem Lett. 2019 May 1;29(9):1060-1064. doi: 10.1016/j.bmcl.2019.03.005.
Fansheng Ran 1,  Yang Liu 2,  Daoguang Zhang 1,  Meixia Liu 1,  Guisen Zhao 3
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Culture West Road, Jinan 250012, PR China.
  • 2 Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • 3 Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Culture West Road, Jinan 250012, PR China. Electronic address: guisenzhao@sdu.edu.cn.
PMID: 30857748 DOI: 10.1016/j.bmcl.2019.03.005
Abstract

Mantle cell lymphoma (MCL) is characterized by the translocation t(11;14) (q13;q32), resulting in the overexpression of cyclin-D1. The progression of MCL is an interaction of multitarget and multilink regulation. It has been proven that Bruton's tyrosine kinase (Btk) is commonly overexpressed in MCL, which makes it a focus of targeted therapy for MCL. Irreversible inhibitors usually have great potency, rapid onset of inhibition and long duration of drug action. Herein, structural modification via an open-loop strategy based on lead compound ibrutinib (IBN) was performed, leading to a series of pyrazole derivatives. Compounds 19c, 19'c, 21c and 21'c showed potent effect in MCL cells with IC50 values lower than 1 μM, and a more than 3-28-fold increase in antiproliferative activity compared with IBN.

Keywords

Anticancer; BTK; Irreversible inhibitors; Mantle cell lymphoma; Pyrazole derivatives.

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