| Literature DB >> 31749910 |
Eddy W Yue1, Yun-Long Li1, Brent Douty1, Chunhong He1, Song Mei1, Brian Wayland1, Thomas Maduskuie1, Nikoo Falahatpisheh1, Richard B Sparks1, Padmaja Polam1, Wenyu Zhu1, Joseph Glenn1, Hao Feng1, Ke Zhang1, Yanlong Li1, Xin He1, Kamna Katiyar1, Maryanne Covington1, Patricia Feldman1, Niu Shin1, Kathy He Wang1, Sharon Diamond1, Yu Li1, Holly K Koblish1, Leslie Hall1, Peggy Scherle1, Swamy Yeleswaram1, Chu-Biao Xue1, Brian Metcalf1, Andrew P Combs1, Wenqing Yao1.
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.Entities:
Year: 2019 PMID： 31749910 PMCID： PMC6862339 DOI： 10.1021/acsmedchemlett.9b00334
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345