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ID: ALA5223170
Journal: ACS Med Chem Lett
Title: Potent and Selective Biaryl Amide Inhibitors of Hematopoietic Progenitor Kinase 1 (HPK1).
Authors: Sokolsky A, Vechorkin O, Hummel JR, Styduhar ED, Wang A, Nguyen MH, Ye HF, Liu K, Zhang K, Pan J, Ye Q, Atasoylu O, Behshad E, He X, Conlen P, Stump K, Ye M, Diamond S, Covington M, Yeleswaram S, Yao W.
Abstract: Herein we report the discovery of a novel biaryl amide series as selective inhibitors of hematopoietic protein kinase 1 (HPK1). Structure-activity relationship development, aided by molecular modeling, identified indazole 5b as a core for further exploration because of its outstanding enzymatic and cellular potency coupled with encouraging kinome selectivity. Late-stage manipulation of the right-hand aryl and amine moieties surmounted issues of selectivity over TRKA, MAP4K2, and STK4 as well as generating compounds with balanced in vitro ADME profiles and promising pharmacokinetics.
CiteXplore: 36655134