1. Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-γ Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate
- Author
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Christian M. Martin, Jennifer Proctor, Patrick O'Hearn, Janid A. Ali, Andre Lescarbeau, Jennifer Hoyt, Jonathan P. DiNitto, Ann M. Rowley, Thomas T. Tibbitts, Catherine A. Evans, Martin R. Tremblay, Tao Liu, Vito J. Palombella, John Soglia, Johan A. Pradeilles, Somarajan J. Nair, Melissa Pink, David G. Winkler, Stanley Goldstein, Quentin Glenadel, Erin L. O’Hearn, Culver Cheung, Erin Brophy, Alfredo C. Castro, and Louis Grenier
- Subjects
0301 basic medicine ,Phosphoinositide 3-kinase ,biology ,Kinase ,Organic Chemistry ,Pharmacology ,Biochemistry ,03 medical and health sciences ,030104 developmental biology ,Pharmacokinetics ,In vivo ,hemic and lymphatic diseases ,Drug Discovery ,biology.protein ,NEUTROPHIL MIGRATION ,Clinical evaluation ,PI3K/AKT/mTOR pathway - Abstract
Optimization of isoquinolinone PI3K inhibitors led to the discovery of a potent inhibitor of PI3K-γ (26 or IPI-549) with >100-fold selectivity over other lipid and protein kinases. IPI-549 demonstrates favorable pharmacokinetic properties and robust inhibition of PI3K-γ mediated neutrophil migration in vivo and is currently in Phase 1 clinical evaluation in subjects with advanced solid tumors.
- Published
- 2016
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