OATD-02 is an orally active, competitive, reversible, noncovalent dual inhibitor of Arginase 1 and Arginase 2 that exhibits slow dissociation kinetics and nanomolar potency across human and murine arginases, effectively reversing arginase-mediated tumor immunosuppression and enabling mechanistic studies in melanoma immunotherapy research.

In enzymatic assays, OATD-02 inhibited recombinant human ARG1/ARG2 (IC50 20/39 nM) and rodent ARG1 variants. In cellular models, it inhibited human ARG2 in CHO-K1 cells (IC50 171.6 nM) and mouse ARG in bone marrow macrophages (IC50 912.9 nM), while showing a significantly higher IC50 (13 mM) for ARG1 in human primary hepatocytes [1].

Oral administration of OATD-02 (10 mg/kg) demonstrates bioavailability of 13% in mice, 30% in rats, and 61% in dogs. A dosage of 5 mg/kg maintained a 4-fold increase in plasma L-arginine levels one week after treatment cessation. In a B16F10 orthotopic melanoma model, treatment with OATD-02 (50 mg/kg, twice daily, p.o.) for 15 days resulted in a Tumor Growth Inhibition (TGI) of 46% [1].