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. 2024 Apr 15:270:116390.
doi: 10.1016/j.ejmech.2024.116390. Epub 2024 Apr 5.

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

Jiamin Zheng  1 , Zhisen Zhang  1 , Xiaoyu Ding  1 , Deheng Sun  1 , Lihua Min  1 , Feng Wang  1 , Sujing Shi  1 , Xin Cai  1 , Man Zhang  1 , Alex Aliper  2 , Feng Ren  1 , Xiao Ding  3 , Alex Zhavoronkov  4
Affiliations

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

Jiamin Zheng et al. Eur J Med Chem. .

Abstract

Protein 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.

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Conflict of interest statement

Declaration of competing interest The authors are all employees of Insilico Medicine. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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