title: Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-γ Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate.
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.
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Evans
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: André
authors.initials: A
authors.lastname: Lescarbeau
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Somarajan J
authors.initials: SJ
authors.lastname: Nair
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Louis
authors.initials: L
authors.lastname: Grenier
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Johan A
authors.initials: JA
authors.lastname: Pradeilles
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Glenadel
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tibbitts
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Rowley
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: DiNitto
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Brophy
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Erin L
authors.initials: EL
authors.lastname: O'Hearn
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Janid A
authors.initials: JA
authors.lastname: Ali
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: David G
authors.initials: DG
authors.lastname: Winkler
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Goldstein
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Patrick
authors.initials: P
authors.lastname: O'Hearn
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Martin
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Hoyt
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: John R
authors.initials: JR
authors.lastname: Soglia
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Culver
authors.initials: C
authors.lastname: Cheung
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Pink
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Proctor
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Vito J
authors.initials: VJ
authors.lastname: Palombella
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Tremblay
authors.affiliation: Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
authors.forename: Alfredo C
authors.initials: AC
authors.lastname: Castro
keywords: IPI-549; PI3K-gamma inhibitor; immuno-oncology; isoform selectivity; neutrophil migration; phosphoinositide-3-kinase