OATD-01 is a highly potent, first-in-class, orally active and selective chitinase inhibitor with low nanomolar activity toward CHIT1 (hCHIT1,IC50=23 nM). OATD-01 shows excellect PK profile in multiple species and is selectivity against a panel of other off-targets. OATD-01 exhibits significant antifibrotic efficacy in vivo and can be used for pulmonary fibrosis (IPF) research[1].
OATD-01 exhibits high affinity toward h/mCHIT1 and h/mAMCase, and the inhibitory constants (Ki) for all four enzymes are 17.3 nM, 26.05 nM, 4.8 nM and 5.7 nM, respectively[1]. These Ki values reveals good correlation with earlier established IC50 data, the IC50 values are 23 nM, 28 nM, 9 nM and 7.8 nM for hCHIT1,mCHIT1, hAMCase and mAMCase, respectively.[1].Off-target in vitro effects of compound OATD-01 have been evaluated at 10 μM in the Eurofins Panlabs panel of 98 in vitro binding and enzymatic assays, involving diverse molecular classes of proteins[1].
OATD-01 (oral gavage; 30 mg/kg, 100 mg/kg; once daily; 21 days) shows significant antifibrotic efficacy in an animal model of bleomycin-induced pulmonary fibrosis. It reduces the degree of lung fibrosis in a dose-dependent manner, ultimately achieving comparable therapeutic efficacy to reference treatment with Nintedanib in this animal model[1].
[1]. Robert Koralewski, et al. Discovery of OATD-01, a First-in-Class Chitinase Inhibitor as Potential New Therapeutics for Idiopathic Pulmonary Fibrosis. J Med Chem. 2020 Dec 24;63(24):15527-15540.