Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-γ Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate

  • ACS Med Chem Lett. 2016 Jul 22;7(9):862-7. doi: 10.1021/acsmedchemlett.6b00238.
Catherine A Evans  1 ,  Tao Liu  1 ,  André Lescarbeau  1 ,  Somarajan J Nair  1 ,  Louis Grenier  1 ,  Johan A Pradeilles  1 ,  Quentin Glenadel  1 ,  Thomas Tibbitts  1 ,  Ann M Rowley  1 ,  Jonathan P DiNitto  1 ,  Erin E Brophy  1 ,  Erin L O'Hearn  1 ,  Janid A Ali  1 ,  David G Winkler  1 ,  Stanley I Goldstein  1 ,  Patrick O'Hearn  1 ,  Christian M Martin  1 ,  Jennifer G Hoyt  1 ,  John R Soglia  1 ,  Culver Cheung  1 ,  Melissa M Pink  1 ,  Jennifer L Proctor  1 ,  Vito J Palombella  1 ,  Martin R Tremblay  1 ,  Alfredo C Castro  1
Affiliations
  • 1. Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
PMID: 27660692 DOI: 10.1021/acsmedchemlett.6b00238
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.

Keywords
IPI-549; PI3K-gamma inhibitor; immuno-oncology; isoform selectivity; neutrophil migration; phosphoinositide-3-kinase.
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