OATD-01 is a novel, selective and highly active CHIT1 (chitinase1, hAMCase IC50=9nM, hCHIT1 IC50=26nM) inhibitor with both an excellent PK profile in multiple species and selectivity against a panel of other off-targets.
Physicochemical Properties
| Molecular Formula | C19H27CLN6O |
| Molecular Weight | 390.910282373428 |
| Exact Mass | 390.193 |
| CAS # | 2088453-21-6 |
| Related CAS # | 2088453-21-6; |
| PubChem CID | 126642132 |
| Appearance | White to off-white solid powder |
| LogP | 3.4 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 27 |
| Complexity | 469 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | C[C@H]1CN([C@H](CO1)CC2=CC=C(C=C2)Cl)C3CCN(CC3)C4=NNC(=N4)N |
| InChi Key | STWVLEKJQQRGMO-GUYCJALGSA-N |
| InChi Code | InChI=1S/C19H27ClN6O/c1-13-11-26(17(12-27-13)10-14-2-4-15(20)5-3-14)16-6-8-25(9-7-16)19-22-18(21)23-24-19/h2-5,13,16-17H,6-12H2,1H3,(H3,21,22,23,24)/t13-,17-/m0/s1 |
| Chemical Name | 3-[4-[(2S,5S)-5-[(4-chlorophenyl)methyl]-2-methylmorpholin-4-yl]piperidin-1-yl]-1H-1,2,4-triazol-5-amine |
| Synonyms | OATD-01OATD01OATD 01 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | The inhibitory concentrations (Ki) of the four enzymes are 17.3 nM, 26.05 nM, 4.8 nM, and 5.7 nM, respectively, and OATD-01 has significant affinity for h/mCHIT1 and h/mAMCase [1]. The IC50 values of 23 nM, 28 nM, 9 nM, and 7.8 nM for hCHIT1, mCHIT1, hAMCase, and mAMCase, respectively, are in good correlation with these Ki values [1]. The external evaluation of the off-target effects of Eurofins Panlabs panlabs Compound OATD-01 was conducted in 98 in vitro binding and enzymatic experiments at 10 μM, involving proteins from several molecular classes [1]. |
| ln Vivo | In an animal model of bleomycin-induced lung fibrosis, OATD-01 (oral gavage; 30 mg/kg, 100 mg/kg; once daily; 21 days) demonstrated a strong anti-fibrotic effectiveness. |
| Animal Protocol |
Animal/Disease Models: Female balb/c (Bagg ALBino) mouse [1] Doses: 30 mg/kg, 100 mg/kg Route of Administration: po (oral gavage); the degree of pulmonary fibrosis was finally achieved in this animal model to achieve treatment effects comparable to Nintedanib treatment [1]. 30 mg/kg, 100 mg/kg; one time/day; 21-day Experimental Results: diminished pulmonary fibrosis in the body[1] |
| References |
[1]. 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. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~255.81 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.40 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.40 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.40 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5581 mL | 12.7907 mL | 25.5813 mL | |
| 5 mM | 0.5116 mL | 2.5581 mL | 5.1163 mL | |
| 10 mM | 0.2558 mL | 1.2791 mL | 2.5581 mL |