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

Abstract：

: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.

journal_name

ACS Med Chem Lett

journal_title

ACS medicinal chemistry letters

authors

Yue EW,Li YL,Douty B,He C,Mei S,Wayland B,Maduskuie T,Falahatpisheh N,Sparks RB,Polam P,Zhu W,Glenn J,Feng H,Zhang K,Li Y,He X,Katiyar K,Covington M,Feldman P,Shin N,Wang KH,Diamond S,Li Y,Koblish HK,Hall

doi

10.1021/acsmedchemlett.9b00334

subject

Has Abstract

pub_date

2019-10-17 00:00:00

pages

1554-1560

issue

11

issn

1948-5875

journal_volume

10

pub_type

杂志文章

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