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Discovery of a novel, potent and selective small-molecule inhibitor of PD-1/PD-L1 interaction with robust in vivo anti-tumour efficacy

Br J Pharmacol. 2021-03; 
Chenglong Liu, Feilong Zhou, Ziqin Yan, Lian Shen, Xichen Zhang, Fenglian He, Heng Wang, Xiaojie Lu, Ker Yu, Yujun Zhao, Di Zhu
Products/Services Used Details Operation
Recombinant Proteins … Biacore Assay hPD-L1(Genscript, Z03371), hPD-L2(Genscript, Z03417) or hPD-1 (Genscript, Z03370) were immobilized on a CM5 chip (GE Health) by using Biaocre T200. Page 15 … (Minneapolis, MN, USA). hPD-1, hPD-L1, and h-PD-L2 were from Genscript(Nanjing, China) … Get A Quote

摘要

objective: PD-1/PD-L1 antibodies have achieved great success in clinical treatment. However, monoclonal antibody drugs also have challenges, such as high manufacturing costs, poor diffusion, low oral bioavailability and limited penetration into tumour tissue. The development of small-molecule inhibitors of PD-1/PD-L1 interaction represents a promising perspective to overcome the above challenges in cancer immunotherapy. methods: We explored structural activity relationships and used biochemical assays to generate a lead compound (ZE132). CD8+ T-cells killing assay and Ifng expression assay were used to verify the in vitro cellular activity of ZE132. Off-target study was performed to verify the selectivity. Syng... More

关键词

PD-1/PD-L1, TGF-β, immunotherapy, tumour immune microenvironment