Compound class:
Synthetic organic
Comment: S4-1 is reported as a small molecule inhibitor of the PD-1/PD-L1 inhibitory immune checkpoint [1] that is exploited for cancer immunotherapy. It promotes dimerisation and internalisation of PD-L1 which reduces the opportunity of signaling via interaction with PD-1. As predicted, S4-1-induced PD-L1/PD-1 pathway blockade promotes T cell activation and reverses the immune inhibitory tumour microenvironment. In vivo, it has demonstrated anti-tumour effects in lung and colorectal cancer models (following intraperitoneal administration). Such small molecules are envisaged as alternatives to the existing anti-PD-L1 and anti-PD-1 monoclonal antibody therapeutics.
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References |
1. Sun C, Yin M, Cheng Y, Kuang Z, Liu X, Wang G, Wang X, Yuan K, Min W, Dong J et al.. (2023)
Novel Small-Molecule PD-L1 Inhibitor Induces PD-L1 Internalization and Optimizes the Immune Microenvironment. J Med Chem, 66 (3): 2064-2083. [PMID:36579489] |