title: Potent, Selective, and Orally Bioavailable Inhibitors of VPS34 Provide Chemical Tools to Modulate Autophagy in Vivo.
abstract: Autophagy is a dynamic process that regulates lysosomal-dependent degradation of cellular components. Until recently the study of autophagy has been hampered by the lack of reliable pharmacological tools, but selective inhibitors are now available to modulate the PI 3-kinase VPS34, which is required for autophagy. Here we describe the discovery of potent and selective VPS34 inhibitors, their pharmacokinetic (PK) properties, and ability to inhibit autophagy in cellular and mouse models.
authors.affiliation: Novartis Institutes for BioMedical Research , 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Ayako
authors.initials: A
authors.lastname: Honda
authors.affiliation: Novartis Institutes for BioMedical Research , 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Edmund
authors.initials: E
authors.lastname: Harrington
authors.affiliation: Novartis Institutes for BioMedical Research , 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Ivan
authors.initials: I
authors.lastname: Cornella-Taracido
authors.affiliation: Novartis Institutes for BioMedical Research , Novartis Campus, CH-4056 Basel, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Furet
authors.affiliation: Novartis Institutes for BioMedical Research , 4560 Horton Street, Emeryville, California 94608, United States.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Knapp
authors.affiliation: Novartis Institutes for BioMedical Research , 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Meir
authors.initials: M
authors.lastname: Glick
authors.affiliation: Novartis Institutes for BioMedical Research , 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Ellen
authors.initials: E
authors.lastname: Triantafellow
authors.affiliation: Novartis Institutes for BioMedical Research , 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: William E
authors.initials: WE
authors.lastname: Dowdle
authors.affiliation: Novartis Institutes for BioMedical Research , 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Wiedershain
authors.affiliation: Novartis Institutes for BioMedical Research , 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Wieslawa
authors.initials: W
authors.lastname: Maniara
authors.affiliation: Novartis Institutes for BioMedical Research , 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Christine
authors.initials: C
authors.lastname: Moore
authors.affiliation: Novartis Institutes for BioMedical Research , 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Finan
authors.affiliation: Novartis Institutes for BioMedical Research , 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Hamann
authors.affiliation: Novartis Institutes for BioMedical Research , 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Brant
authors.initials: B
authors.lastname: Firestone
authors.affiliation: Novartis Institutes for BioMedical Research , 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Leon O
authors.initials: LO
authors.lastname: Murphy
authors.affiliation: Novartis Institutes for BioMedical Research , 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Erin P
authors.initials: EP
authors.lastname: Keaney
keywords: VPS34; autophagy; phosphoinositide 3-kinase
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