2. Academic Validation
  3. Synthesis and structure-activity optimization of azepane-containing derivatives as PTPN2/PTPN1 inhibitors

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

  • Eur J Med Chem. 2024 Apr 15:270:116390. doi: 10.1016/j.ejmech.2024.116390.
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

Affiliations

  • 1 Insilico Medicine Shanghai Ltd, Suite 901, Tower C, Changtai Plaza, 2889 Jinke Road, Pudong New District, Shanghai, 201203, China.
  • 2 Insilico Medicine AI Limited, Masdar City, Abu Dhabi, 145748, United Arab Emirates.
  • 3 Insilico Medicine Shanghai Ltd, Suite 901, Tower C, Changtai Plaza, 2889 Jinke Road, Pudong New District, Shanghai, 201203, China. Electronic address: xiao.ding@insilico.ai.
  • 4 Insilico Medicine Shanghai Ltd, Suite 901, Tower C, Changtai Plaza, 2889 Jinke Road, Pudong New District, Shanghai, 201203, China; Insilico Medicine AI Limited, Masdar City, Abu Dhabi, 145748, United Arab Emirates. Electronic address: alex@insilico.com.
PMID: 38604096 DOI: 10.1016/j.ejmech.2024.116390
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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