OATD-01 是一种高效、口服活性、 first-in-class、选择性几丁质酶 (chitinase) 抑制剂，对 CHIT1 具有低纳摩尔活性 (hCHIT1, IC50=23 nM)。OATD-01 在多个物种中显示出良好的药代动力学特征。OATD-01 在体内具有显著的抗纤维化活性，用于肺纤维化 (IPF) 研究。
货号:ajcx33106
CAS:2088453-21-6
分子式:C19H27ClN6O
分子量：390.91
溶解度:DMSO : 100 mg/mL (255.81 mM; Need ultrasonic)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

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.