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

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

  • ACS Med Chem Lett. 2019 Oct 17;10(11):1554-1560. doi: 10.1021/acsmedchemlett.9b00334.
Eddy W Yue 1,  Yun-Long Li 1,  Brent Douty 1,  Chunhong He 1,  Song Mei 1,  Brian Wayland 1,  Thomas Maduskuie 1,  Nikoo Falahatpisheh 1,  Richard B Sparks 1,  Padmaja Polam 1,  Wenyu Zhu 1,  Joseph Glenn 1,  Hao Feng 1,  Ke Zhang 1,  Yanlong Li 1,  Xin He 1,  Kamna Katiyar 1,  Maryanne Covington 1,  Patricia Feldman 1,  Niu Shin 1,  Kathy He Wang 1,  Sharon Diamond 1,  Yu Li 1,  Holly K Koblish 1,  Leslie Hall 1,  Peggy Scherle 1,  Swamy Yeleswaram 1,  Chu-Biao Xue 1,  Brian Metcalf 1,  Andrew P Combs 1,  Wenqing Yao 1
Affiliations

Affiliation

  • 1 Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, Delaware 19803, United States.
PMID: 31749910 DOI: 10.1021/acsmedchemlett.9b00334
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.

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