NP19

 NP19 is a novel and potent inhibitor of the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 (PD-1/PD-L1) Interaction with IC50 of 12 nM in homogeneous time-resolved fluorescence (HTRF) binding assays. NP19 dose-dependently elevated IFN-γ production in a coculture model of Hep3B/OS-8/hPD-L1 and CD3 T cells. Furthermore, NP19 displayed significant in vivo antitumor efficacy in two different mouse models of cancer (a melanoma B16-F10 tumor model and an H22 hepatoma tumor model). Moreover, H&E staining and flow cytometry data suggested that NP19 activated the immune microenvironment in the tumor, which may contribute to its antitumor effects. This work shows NP19 is a promising lead compound for further development as a new generation of small molecule inhibitors targeting the PD-1/PD-L1 pathway.

References: J Med Chem. 2020 Aug 13;63(15):8338-8358. doi: 10.1021/acs.jmedchem.0c00574.

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