| Literature DB >> 32551005 |
Gleb Andryianau1, Michal Kowalski1, Michal C Piotrowicz1, Adam A Rajkiewicz1,2, Barbara Dymek1, Piotr L Sklepkiewicz1, Elzbieta Pluta1, Filip Stefaniak1,3, Wojciech Czestkowski1, Sylwia Olejniczak1, Marzena Mazur1, Piotr Niedziejko1, Robert Koralewski1, Krzysztof Matyszewski1, Mariusz Gruza1, Agnieszka Zagozdzon1, Magdalena Salamon1, Aleksandra Rymaszewska1, Mikolaj Welzer1, Karolina Dzwonek1, Jakub Golab1,4, Jacek Olczak1, Agnieszka Bartoszewicz1, Adam Golebiowski1.
Abstract
Human acidic mammalian chitinase (hAMCase) is one of two true chitinases in humans, the function of which remains elusive. In addition to the defense against highly antigenic chitin and chitin-containing pathogens in the gastric and intestinal contents, AMCase has been implicated in asthma, allergic inflammation, and ocular pathologies. Potent and selective small-molecule inhibitors of this enzyme have not been identified to date. Here we describe structural modifications of compound OAT-177, a previously developed inhibitor of mouse AMCase, leading to OAT-1441, which displays high activity and selectivity toward hAMCase. Significantly reduced off-target activity toward the human ether-à-go-go-related gene (hERG) and a good pharmacokinetic profile make OAT-1441 a potential candidate for further preclinical development as well as a useful tool compound to study the physiological role of hAMCase.Entities:
Year: 2020 PMID： 32551005 PMCID： PMC7294726 DOI： 10.1021/acsmedchemlett.0c00092
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345