ORIC-533 

ORIC-533 is an orally active, highly selective, AMP-competitive CD73 inhibitor that potently blocks adenosine production with sub-nanomolar affinity (K_a=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].

ORIC-533 (0.01-1.0 μM; 3-4 days) exerts dose-dependent killing effects on autologous CD138⁺ multiple myeloma cells in bone marrow mononuclear cell culture systems derived from patients with relapsed/refractory multiple myeloma, with the maximal activity observed at the concentration of 1.0 μM after 3-4 days of treatment^[1].
ORIC-533 (0.01-0.1 μM; 15 min) reduces adenosine production in bone marrow aspirate plasma supernatants from patients with relapsed/refractory multiple myeloma in a dose-dependent manner, with significant inhibitory effects observed at concentrations of 0.01 μM and 0.1 μM after 15 min of incubation^[1].
ORIC-533 (0.5 μM; treated for 7-10 days after 2 days of CD3/CD28 stimulation) significantly upregulates the central memory, effector memory, and terminally differentiated effector memory T cell subsets in bone marrow mononuclear cells from multiple myeloma patients following CD3/CD28 stimulation^[1].
ORIC-533 (0.5 μM; 3-4 d) induces immunogenic cell death in autologous CD138+ multiple myeloma cells, upregulates cell surface calreticulin (Calreticulin) expression and promotes the extracellular release of high mobility group box 1 (HMGB1) in bone marrow mononuclear cell culture systems derived from patients with multiple myeloma^[1].
ORIC-533 (0.5 μM; 24 h) activates plasmacytoid dendritic cells from patients with multiple myeloma, as evidenced by the upregulated expression of activation and maturation markers CD40, CD80, CD83, CD86, and HLA-DR^[1].
ORIC-533 (0.5 μM; 2 d) enhances the expression level of CD69 during the activation of CD3+ T cells in the pDC-T cell co-culture system derived from patients with multiple myeloma, which is verified by the increased CD69 expression and the elevated proportion of activated T cells on CD3+ T cells^[1].
ORIC-533 (0.5 μM; with bone marrow mononuclear cells for 3 days, co-cultured with U266 cells for 1 day) reduces the viability of HLA-A2⁺ U266 multiple myeloma cells, and exerts a synergistic effect with daratumumab (HY-P9915)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

ORIC-533 upregulates the expression of calreticulin on the surface of multiple myeloma cells and increases the level of high-mobility group box 1 (HMGB1), thereby inducing immunogenic cell death (ICD). Meanwhile, ORIC-533 upregulates the activation and maturation markers of plasmacytoid dendritic cells, promotes the proliferation of CD3⁺ T cells and the expression of the activation marker CD69, increases the proportions of central memory T cells and effector memory T cells, and ultimately restores natural killer cell-mediated cytotoxicity to eliminate tumors^[1].
ORIC-533 (150 mg/kg; p.o.; once daily; for 21 consecutive days) achieves a 67% tumor growth inhibition rate in C57BL/6 mice bearing E.G7-OVA tumors, while increasing the intratumoral level and proliferative capacity of CD8⁺ T cells^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

605.93

C₂₀H₂₉ClN₉O₉P

2641306-62-7

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

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [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]