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ChemicalBook >> journal list >> Journal of Enzyme Inhibition and Medicinal Chemistry >>article
Journal of Enzyme Inhibition and Medicinal Chemistry

Journal of Enzyme Inhibition and Medicinal Chemistry

IF: 5.6
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PD-L1 dimerisation induced by biphenyl derivatives mediates anti-breast cancer activity via the non-immune PD-L1–AKT–mTOR/Bcl2 pathway

Published:1 December 2023 DOI: 10.1080/14756366.2023.2230388 PMID: 37439326
Hua Zhang, Shi-Jia Zhou, Chen-Feng Shen, Yong-Nan Zhou, Cai-Yun Wu, Meng-Yu Zhu, Qi-Meng Yu, Annoor Awadasseid, Yan-Ling Wu, Wen Zhang

Abstract

Recent studies on biphenyl-containing compounds, a type of PD-1/PD-L1 blocker which binds to PD-L1 and induces dimerisation, have focussed on its immune function. Herein, 10 novel biphenyl derivatives were designed and synthesised. The results of the CCK-8 showed that compounds have different anti-tumour activities for tumour cells in the absence of T cells. Particularly, 12j-4 can significantly induce the apoptosis of MDA-MB-231 cells (IC50?=?2.68?±?0.27?μM). In further studies, 12j-4 has been shown to prevent the phosphorylation of AKT by binding to cytoplasmic PD-L1, which induces apoptosis in MDA-MB-231 cells through non-immune pathways. The inhibition of AKT phosphorylation restores the activity of GSK-3β, ultimately resulting in the degradation of PD-L1. Besides, in?vivo study indicated that 12j-4 repressed tumour growth in nude mice. As these biphenyls exert their anti-tumour effects mainly through non-immune pathways, they are worthy of further study as PD-L1 inhibitors.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
PD-L1 inhibitor 1 1675203-84-5 C25H29N3O3 129 suppliers $12.00-$1600.00
PD-L1 inhibitor 1 1675203-84-5 C25H29N3O3 129 suppliers $12.00-$1600.00
PD-L1 inhibitor 1 1675203-84-5 C25H29N3O3 129 suppliers $12.00-$1600.00
PD-L1 inhibitor 1 1675203-84-5 C25H29N3O3 129 suppliers $12.00-$1600.00

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