CD73 Inhibitor

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.

MethADP (sodium salt) (Adenosine 5'-(α,β-methylene)diphosphate (sodium)) is a specific CD73 inhibitor.

PSB-24000 (Compound 27) is a selective ecto-5'-nucleotidase (CD73) inhibitor with a K_i value of 563 nM against human CD73 (K_i= 481 nM at membrane-bound CD73 in triple-negative breast cancer cells). PSB-24000 interferes with CD73's recognition and action on the substrate AMP, and prevents the generation of immunosuppressive and cancer-promoting adenosine from AMP. PSB-24000 is promising for research of cancers.

CD73-IN-11 (compound 24) is a potent inhibitor of CD73. CD73 can catalyze the production of adenosine from extracellular 5'-phosphate adenosine (5'-AMP), and adenosine can induce immunosuppressive effects and promote tumor proliferation and/or metastasis. CD73-IN-11 can be used for the study of tumor-related diseases.

CD73-IN-2 is a potent CD73 inhibitor extracted from WO2020151707A1, example 1, has an IC₅₀ of 0.09 nM.

CD73-IN-19 (Compound 4ab) is a CD73 inhibitor (with a 44% inhibition rate of CD73 enzymatic activity at 100 μM). CD73-IN-19 (at 10 μM and 100 μM) can completely antagonize the blockade of T cell proliferation induced by TCR (T cell receptor) triggering (which is induced by CD73 activity), and it can also inhibit the hA2A receptor activity in HEK-293 cells (K_i is 3.31 μM). CD73-IN-19 holds promise for research in the field of immune diseases.

CD73-IN-10 (compound 4) is a potent inhibitor of CD73. CD73 can catalyze the production of adenosine from extracellular 5'-phosphate adenosine (5'-AMP), and adenosine can induce immunosuppressive effects and promote tumor proliferation and/or metastasis. CD73-IN-10 can be used for the study of tumor-related diseases.

CD73-IN-13 (compound 7) is a potent inhibitor of CD73. CD73 is closely associated with tumor growth, angiogenesis and metastasis. CD73-IN-13 can be used for the study of tumor-related diseases.

CD73-IN-20 (Compound 5c) is an e5′NT (CD73) inhibitor (IC₅₀: 0.37 μM). CD73-IN-20 also inhibits other ectonucleotidases, with IC₅₀s of 1.12 μM (h-ENPP1), 1.37 μM (h-ENPP3), 1.66 μM (r-e5′NT), 1.48 μM (h-TNAP), respectively. CD73-IN-20 can be used for cancer research.

CD73-IN-8 (compound 57) is a potent inhibitor of CD73. CD73 can catalyze the production of adenosine from extracellular 5'-phosphate adenosine (5'-AMP), and adenosine can induce immunosuppressive effects and promote tumor proliferation and/or metastasis. CD73-IN-8 can be used for the study of tumor-related diseases.

GMPCP (GpCp) trisodium (Compound 7 trisodium) is a guanosine derivative is a CD73 inhibitor, with K_is of 1110 nM (rat soluble CD73) and 410 nM (human soluble CD73) respectively. GMPCP (GpCp) trisodium can be used for research of cancer.

D73-IN-14 is a potent, selective and orally active CD73 inhibitor with an IC₅₀ value of 0.17 nM. CD73-IN-14 increases the number of tumor-infiltrating CD8⁺ cells and shows anti-tumor activity. CD73-IN-14 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

ZM522 is a CD73 inhibitor with an IC₅₀ value of 0.56 μM. ZM522 effectively increases the levels of interferon-γ (INF-γ) and enhances immune activity by regulating the activation status of T cells. ZM522 holds promise for research in the fields of immunology and cancer therapy.

XC-12 is an orally active and potent small-molecule CD73 inhibitor (an immune checkpoint) with IC₅₀ values of 12.36 nM and 1.29 nM against soluble and membrane-bound CD73 forms, respectively. XC-12 is promising for research of cancers.

MethADP (Adenosine 5'-(α,β-methylene)diphosphate) trisodium is a CD73 inhibitor. MethADP trisodium can be used for the research of ATP-adenosine pathway.

CD73-IN-17 (compound 19) is a CD73 inhibitor with IC₅₀ of 0.1 μM for hCD73. CD73-IN-17 can be used in anti-cancer research.

COPCP trisodium (Compound 7a) is a potent and selective ecto-5'-nucleotidase CD73 inhibitor. COPCP trisodium blocks CD73-mediated adenosine production, reducing the inhibitory effect of adenosine on immune cells. COPCP trisodium is promising for research of cancers.

MRS4620 is a potent CD73 inhibitor, with a K_i of 0.436 nM. MRS4620 can be use for the research of cancer immunoresearch.

CD73-IN-9 (compound 2) is a potent inhibitor of CD73. CD73 can catalyze the production of adenosine from extracellular 5'-phosphate adenosine (5'-AMP), and adenosine can induce immunosuppressive effects and promote tumor proliferation and/or metastasis. CD73-IN-9 can be used for the study of tumor-related diseases.

CD73-IN-22 (Compound HX-6) is a non-nucleoside CD73 inhibitor with an IC₅₀ of 0.07 μM. When radiolabeled with ⁶⁸Ga, CD73-IN-22 acts as a PET radiotracer for detecting CD73 expression. When radiolabeled with ¹⁷⁷Lu, CD73-IN-22 exhibits anticancer activity against colorectal adenocarcinoma. CD73-IN-22 is applicable to research related to colon adenocarcinoma and breast cancer.