INCB050465 (Parsaclisib), a Novel Next-Generation Inhibitor of Phosphoinositide 3-Kinase Delta (PI3Kδ).

Autor:	Yue EW; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Li YL; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Douty B; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., He C; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Mei S; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Wayland B; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Maduskuie T; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Falahatpisheh N; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Sparks RB; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Polam P; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Zhu W; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Glenn J; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Feng H; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Zhang K; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Li Y; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., He X; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Katiyar K; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Covington M; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Feldman P; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Shin N; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Wang KH; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Diamond S; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Li Y; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Koblish HK; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Hall L; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Scherle P; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Yeleswaram S; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Xue CB; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Metcalf B; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Combs AP; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States., Yao W; Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States.
Jazyk:	angličtina
Zdroj:	ACS medicinal chemistry letters [ACS Med Chem Lett] 2019 Oct 17; Vol. 10 (11), pp. 1554-1560. Date of Electronic Publication: 2019 Oct 17 (Print Publication: 2019).
DOI:	10.1021/acsmedchemlett.9b00334
Abstrakt:	A medicinal chemistry effort focused on identifying a structurally diverse candidate for phosphoinositide 3-kinase delta (PI3Kδ) led to the discovery of clinical candidate INCB050465 ( 20 , parsaclisib). The unique structure of 20 contains a pyrazolopyrimidine hinge-binder in place of a purine motif that is present in other PI3Kδ inhibitors, such as idelalisib ( 1 ), duvelisib ( 2 ), and INCB040093 ( 3 , dezapelisib). Parsaclisib ( 20 ) is a potent and highly selective inhibitor of PI3Kδ with drug-like ADME properties that exhibited an excellent in vivo profile as demonstrated through pharmacokinetic studies in rats, dogs, and monkeys and through pharmacodynamic and efficacy studies in a mouse Pfeiffer xenograft model. Competing Interests: The authors declare no competing financial interest. (Copyright © 2019 American Chemical Society.)
Databáze:	MEDLINE
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