Synthesis and structure-activity optimization of azepane-containing derivatives as PTPN2/PTPN1 inhibitors

Eur J Med Chem. 2024 Apr 5;270:116390. doi: 10.1016/j.ejmech.2024.116390. Online ahead of print.ABSTRACTProtein tyrosine phosphatases PTPN2 and PTPN1 (also known as PTP1B) have been implicated in a number of intracellular signaling pathways of immune cells. The inhibition of PTPN2 and PTPN1 has emerged as an attractive approach to sensitize T cell anti-tumor immunity. Two small molecule inhibitors have been entered the clinic. Here we report the design and development of compound 4, a novel small molecule PTPN2/N1 inhibitor demonstrating nanomolar inhibitory potency, good in vivo oral bioavailability, and robust in vivo antitumor efficacy.PMID:38604096 | DOI:10.1016/j.ejmech.2024.116390

Source: European Journal of Medicinal Chemistry - April 11, 2024 Category: Chemistry Authors: Jiamin Zheng Zhisen Zhang Xiaoyu Ding Deheng Sun Lihua Min Feng Wang Sujing Shi Xin Cai Man Zhang Alex Aliper Feng Ren Xiao Ding Alex Zhavoronkov Source Type: research