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• W3100545535 abstract "A series of novel linear aliphatic amine-linked triaryl derivatives as inhibitors of PD-1/PD-L1 were designed, synthesized, and evaluated in vitro and in vivo. In this chemical series, compound 58 showed the most potent inhibitory activity and binding affinity with hPD-L1, with an IC50 value of 12 nM and a KD value of 16.2 pM, showing a binding potency approximately 2000-fold that of hPD-1. Compound 58 could bind with hPD-L1 on the cellular surface and competitively block the interaction of hPD-1 with hPD-L1. In a T cell function assay, 58 restored the T cell function, leading to increased IFN-γ secretion. Moreover, in a humanized mouse model, compound 58 significantly inhibited tumor growth without obvious toxicity and showed moderate PK properties after intravenous injection. These results indicated that 58 is a promising lead for further development of small-molecule PD-1/PD-L1 inhibitors for cancer therapy." @default.
• W3100545535 created "2020-11-23" @default.
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• W3100545535 date "2020-11-13" @default.
• W3100545535 modified "2023-10-17" @default.
• W3100545535 title "Design, Synthesis, and Biological Evaluation of Linear Aliphatic Amine-Linked Triaryl Derivatives as Potent Small-Molecule Inhibitors of the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Interaction with Promising Antitumor Effects In Vivo" @default.
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• W3100545535 doi "https://doi.org/10.1021/acs.jmedchem.0c01329" @default.
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