6ZE8
Crystal structure of human chitotriosidase-1 (hCHIT) catalytic domain in complex with compound OATD-01
Summary for 6ZE8
| Entry DOI | 10.2210/pdb6ze8/pdb |
| Descriptor | Chitotriosidase-1, 5-(4-((2S,5S)-5-(4-chlorobenzyl)-2-methylmorpholino)piperidin-1-yl)-4H-1,2,4-triazol-3-amine, SODIUM ION, ... (5 entities in total) |
| Functional Keywords | chitinase, chitin binding, hydrolase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 6 |
| Total formula weight | 247283.66 |
| Authors | Nowotny, M.,Bartlomiejczak, A.,Napiorkowska-Gromadzka, A. (deposition date: 2020-06-16, release date: 2020-11-11, Last modification date: 2024-10-23) |
| Primary citation | Koralewski, R.,Dymek, B.,Mazur, M.,Sklepkiewicz, P.,Olejniczak, S.,Czestkowski, W.,Matyszewski, K.,Andryianau, G.,Niedziejko, P.,Kowalski, M.,Gruza, M.,Borek, B.,Jedrzejczak, K.,Bartoszewicz, A.,Pluta, E.,Rymaszewska, A.,Kania, M.,Rejczak, T.,Piasecka, S.,Mlacki, M.,Mazurkiewicz, M.,Piotrowicz, M.,Salamon, M.,Zagozdzon, A.,Napiorkowska-Gromadzka, A.,Bartlomiejczak, A.,Mozga, W.,Dobrzanski, P.,Dzwonek, K.,Golab, J.,Nowotny, M.,Olczak, J.,Golebiowski, A. Discovery of OATD-01 , a First-in-Class Chitinase Inhibitor as Potential New Therapeutics for Idiopathic Pulmonary Fibrosis. J.Med.Chem., 63:15527-15540, 2020 Cited by PubMed Abstract: Chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase) are the enzymatically active chitinases that have been implicated in the pathology of chronic lung diseases such as asthma and interstitial lung diseases (ILDs), including idiopathic pulmonary fibrosis (IPF) and sarcoidosis. The clinical and preclinical data suggest that pharmacological inhibition of CHIT1 might represent a novel therapeutic approach in IPF. Structural modification of an advanced lead molecule led to the identification of compound (, a highly active CHIT1 inhibitor with both an excellent PK profile in multiple species and selectivity against a panel of other off-targets. given orally once daily in a range of doses between 30 and 100 mg/kg showed significant antifibrotic efficacy in an animal model of bleomycin-induced pulmonary fibrosis. is the first-in-class CHIT1 inhibitor, currently completed phase 1b of clinical trials, to be a potential treatment for IPF. PubMed: 33078933DOI: 10.1021/acs.jmedchem.0c01179 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.5 Å) |
Structure validation
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