Discovery of non-boronic acid Arginase 1 inhibitors through virtual screening and biophysical methods.
Basic Information
ID: ALA5252591
Journal: Bioorg Med Chem Lett
Title: Discovery of non-boronic acid Arginase 1 inhibitors through virtual screening and biophysical methods.
Authors: Gathiaka S, Palte RL, So SS, Chai X, Richard Miller J, Kuvelkar R, Wen X, Cifelli S, Kreamer A, Liaw A, McLaren DG, Fischer C.
Abstract: Inhibiting Arginase 1 (ARG1), a metalloenzyme that hydrolyzes l-arginine in the urea cycle, has been demonstrated as a promising therapeutic avenue in immuno-oncology through the restoration of suppressed immune response in several types of cancers. Most of the currently reported small molecule inhibitors are boronic acid based. Herein, we report the discovery of non-boronic acid ARG1 inhibitors through virtual screening. Biophysical and biochemical methods were used to experimentally profile the hits while X-ray crystallography confirmed a class of trisubstituted pyrrolidine derivatives as optimizable alternatives for the development of novel classes of immuno-oncology agents targeting this enzyme.
CiteXplore: 36822300
DOI: 10.1016/j.bmcl.2023.129193
Patent ID: ┄