50508-27-5Relevant academic research and scientific papers
JAK3 inhibitors based on thieno[3,2-d]pyrimidine scaffold: design, synthesis and bioactivity evaluation for the treatment of B-cell lymphoma
Chi, Fuyun,Chen, Lixue,Wang, Changyuan,Li, Lei,Sun, Xiuli,Xu, Youjun,Ma, Tengyue,Liu, Kexin,Ma, Xiaodong,Shu, Xiaohong
, (2020/01/08)
JAK3 is predominantly expressed in hematopoietic cells and has been a promising therapeutic target for the treatment of B-cell lymphoma. In this study, a new class of thieno[3,2-d]pyrimidines harboring acrylamide pharmacophore were synthesized as potent covalent JAK3 inhibitors (IC50 50 values of 1.9 nM and 1.8 nM, respectively. Furthermore, compared with the reference agents, Spebrutinib and Ibrutinib, 9a not only demonstrated enhanced antiproliferative activity against B lymphoma cells, but also showed very weak proliferative inhibition against normal peripheral blood mononuclear cells (PBMCs) at a concentration of 20 μM. Analysis of the mechanism revealed that 9a could induce the obvious apoptosis in B lymphoma cells and prevent JAK3-STAT3 cascade as well as BTK pathway. Taken together, 9a may be served as a potential new JAK3 inhibitor for the treatment of B-cell lymphoma.
Identification of highly potent BTK and JAK3 dual inhibitors with improved activity for the treatment of B-cell lymphoma
Ge, Yang,Wang, Changyuan,Song, Shijie,Huang, Jiaxin,Liu, Zhihao,Li, Yongming,Meng, Qiang,Zhang, Jianbin,Yao, Jihong,Liu, Kexin,Ma, Xiaodong,Sun, Xiuli
, p. 1847 - 1857 (2017/12/04)
The BTK and JAK3 receptor tyrosine kinases are two validated and therapeutically amenable targets in the treatment of B-cell lymphomas. Here we report the identification of several classes of pyrimidine derivatives as potent BTK and JAK3 dual inhibitors.
