INCB050465 (Parsaclisib), a Novel Next-Generation Inhibitor of Phosphoinositide 3-Kinase Delta (PI3Kδ)
| Autor: | Swamy Yeleswaram, Thomas Maduskuie, Brian Wayland, Hao Feng, Patricia Feldman, Niu Shin, Yanlong Li, Chu-Biao Xue, Peggy Scherle, Song Mei, Kathy Wang, Maryanne Covington, Wenqing Yao, Padmaja Polam, Richard B. Sparks, Wenyu Zhu, Xin He, Sharon Diamond, Eddy W. Yue, Chunhong He, Brian Metcalf, Holly Koblish, Ke Zhang, Nikoo Falahatpisheh, Brent Douty, Leslie Hall, Yu Li, Andrew P. Combs, Joseph Glenn, Kamna Katiyar, Yun-Long Li |
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| Rok vydání: | 2019 |
| Předmět: |
Purine
Phosphoinositide 3-kinase biology 010405 organic chemistry Organic Chemistry Pharmacology 01 natural sciences Biochemistry Duvelisib Pyrazolopyrimidine 0104 chemical sciences 010404 medicinal & biomolecular chemistry chemistry.chemical_compound chemistry Pharmacokinetics In vivo Drug Discovery biology.protein Idelalisib ADME |
| Zdroj: | ACS Med Chem Lett |
| ISSN: | 1948-5875 |
| Popis: | [Image: see text] 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. |
| Databáze: | OpenAIRE |
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