2641306-62-7
Chemical Structure
ORIC-533
- CAS No.: 2641306-62-7
- Formula:C20H29ClN9O9P
- Molecular Weight:605.93
InChIKey: WQAMOSWUARUEOH-GGBXQBQZSA-N
SMILES: O[C@H]1[C@@H](O)[C@H](N2C3=NC(Cl)=NC(NC4CCCC4)=C3C=N2)O[C@@H]1CO[C@](P(O)(O)=O)(CO)COCC5=NN=NN5
Biological Activity: ORIC-533 is an orally active, highly selective, AMP-competitive CD73 inhibitor that potently blocks adenosine production with sub-nanomolar affinity (Ka=0.03 nM). In multiple myeloma, ORIC-533 restores and enhances the cytotoxicity of the immune system against tumor cells through multiple immunological mechanisms, including reversing the immunosuppressive microenvironment, inducing immunogenic cell death, and activating dendritic cells, T cells and NK cells, with no direct toxicity to normal cells. The combination of ORIC-533 with Daratumumab (HY-P9915) synergistically enhances anti-tumor efficacy, significantly increases intratumoral CD8+ T cell infiltration and inhibits tumor growth in vivo[1][2].
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ORIC-533 | ORIC-533 is an orally active, highly selective, AMP-competitive CD73 inhibitor that potently blocks adenosine production with sub-nanomolar affinity (Ka=0.03 nM). In multiple myeloma, ORIC-533 restores and enhances the cytotoxicity of the immune system against tumor cells through multiple immunological mechanisms, including reversing the immunosuppressive microenvironment, inducing immunogenic cell death, and activating dendritic cells, T cells and NK cells, with no direct toxicity to normal cells. The combination of ORIC-533 with Daratumumab (HY-P9915) synergistically enhances anti-tumor efficacy, significantly increases intratumoral CD8+ T cell infiltration and inhibits tumor growth in vivo. | |||||||||||||||||||||
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References
- [1]. Ray A, et al. A novel small molecule inhibitor of CD73 triggers immune-mediated multiple myeloma cell death. Blood Cancer J. 2024;14(1):58. Published 2024 Apr 9. [Content Brief]
- [2]. Moore JT, et al. Discovery of ORIC-533, an Orally Bioavailable CD73 Inhibitor That Maintains Activity in High AMP Environments to Reverse Tumor Immunosuppression. J Med Chem. 2025;68(21):22145-22169. [Content Brief]
