ORIC-533 is a selective, orally active inhibitor of CD73 that operates through an AMP-competitive mechanism, demonstrating potent inhibition of adenosine production with a sub-nanomolar affinity (Ka 0.03 nM). This compound has shown significant promise in the context of multiple myeloma, as it enhances the cytotoxic activity of the immune system against tumor cells by reversing immunosuppression, inducing immunogenic cell death, and activating various immune cells including dendritic cells, T cells, and NK cells, while exhibiting minimal toxicity to normal cells. Furthermore, combined administration of ORIC-533 with daratumumab effectively increases intratumoral CD8+ T cell infiltration and substantially inhibits tumor growth in preclinical models.
ORIC-533 is a selective, orally active inhibitor of CD73 that operates through an AMP-competitive mechanism, demonstrating potent inhibition of adenosine production with a sub-nanomolar affinity (Ka 0.03 nM). This compound has shown significant promise in the context of multiple myeloma, as it enhances the cytotoxic activity of the immune system against tumor cells by reversing immunosuppression, inducing immunogenic cell death, and activating various immune cells including dendritic cells, T cells, and NK cells, while exhibiting minimal toxicity to normal cells. Furthermore, combined administration of ORIC-533 with daratumumab effectively increases intratumoral CD8+ T cell infiltration and substantially inhibits tumor growth in preclinical models.
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