Rapid identification of ETP-46992, orally bioavailable PI3K inhibitor, selective versus mTOR
详细信息 查看全文
- 作者：Sonia Mart¨ªnez Gonz¨¢lez ; Ana Isabel Hern¨¢ndez ; Carmen Varela ; Milagros Lorenzo ; Francisco Ramos-Lima ; Elena Cend¨®n ; David Cebri¨¢n ; Enara Aguirre ; Elena Gomez-Casero ; M.I. Albarr¨¢n ; Patricia Alfonso ; Beatriz Garc¨ªa-Serelde ; Genoveva Mateos ; Julen Oyarzabal ; Obdulia Rabal ; Francisca Mulero ; Teresa Gonzalez-Gr ; a ; Wolfgang Link ; Jes¨²s Fominaya ; Mariano Barbacid ; et al.
- 关键词：PI3K inhibitors ; Imidazo [1 ; 2-a] pyrazines ; Cancer treatment
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：15 August, 2012
- 年：2012
- 卷：22
- 期：16
- 页码：5208-5214
- 全文大小：967 K
文摘
Phosphoinositide-3-kinases (PI3K) are a family of lipid kinases mediating numerous cell processes such as proliferation, migration and differentiation. PI3K is an important target for cancer therapeutics due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein, we describe the rapid identification of ETP-46992, within 2-aminocarbonyl imidazo [1,2-a] pyrazine series, with suitable pharmacokinetic (PK) properties that allows the establishment of mechanism of action and efficacy in vivo studies. ETP-46992 showed tumor growth inhibition in a GEMM mouse tumor model driven by a K-RasG12V oncogenic mutation and in tumor xenograft models with PI3K pathway deregulated (BT474).