Potent, Selective, and Orally Bioavailable Inhibitors of VPS34 Provide Chemical Tools to Modulate Autophagy in Vivo

详细信息    查看全文

• 作者：Ayako Honda ; Edmund Harrington ; Ivan Cornella-Taracido ; Pascal Furet ; Mark S. Knapp ; Meir Glick ; Ellen Triantafellow ; William E. Dowdle ; Dmitri Wiedershain ; Wieslawa Maniara ; Christine Moore ; Peter M. Finan ; Lawrence G. Hamann ; Brant Firestone ; Leon O. Murphy ; Erin P. Keaney
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：January 14, 2016
• 年：2016
• 卷：7
• 期：1
• 页码：72-76
• 全文大小：326K
• ISSN：1948-5875

文摘

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.