Rapid identification of ETP-46992, orally bioavailable PI3K inhibitor, selective versus mTOR |
| |
Authors: | Sonia Martínez González Ana Isabel Hernández Carmen Varela Milagros Lorenzo Francisco Ramos-Lima Elena Cendón David Cebrián Enara Aguirre Elena Gomez-Casero M I Albarrán Patricia Alfonso Beatriz García-Serelde Genoveva Mateos Julen Oyarzabal Obdulia Rabal Francisca Mulero Teresa Gonzalez-Granda Wolfgang Link Jesús Fominaya Mariano Barbacid James R Bischoff Pilar Pizcueta Carmen Blanco-Aparicio Joaquín Pastor |
| |
Affiliation: | Experimental Therapeutics Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, E-28029 Madrid, Spain. |
| |
Abstract: | 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-Ras(G12V) oncogenic mutation and in tumor xenograft models with PI3K pathway deregulated (BT474). |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|