Potent and Selective Biaryl Amide Inhibitors of Hematopoietic Progenitor Kinase 1 (HPK1).

Autor:	Sokolsky A; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Vechorkin O; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Hummel JR; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Styduhar ED; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Wang A; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Nguyen MH; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Ye HF; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Liu K; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Zhang K; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Pan J; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Ye Q; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Atasoylu O; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Behshad E; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., He X; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Conlen P; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Stump K; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Ye M; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Diamond S; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Covington M; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Yeleswaram S; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Yao W; Incyte Research Institute, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States.
Jazyk:	angličtina
Zdroj:	ACS medicinal chemistry letters [ACS Med Chem Lett] 2022 Dec 13; Vol. 14 (1), pp. 116-122. Date of Electronic Publication: 2022 Dec 13 (Print Publication: 2023).
DOI:	10.1021/acsmedchemlett.2c00241
Abstrakt:	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. Competing Interests: The authors declare the following competing financial interest(s): All of the authors are current or former employees of Incyte Corporation. (© 2022 American Chemical Society.)
Databáze:	MEDLINE
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