Discovery of a Phosphoinositide 3-Kinase (PI3K) β/δ Inhibitor for the Treatment of Phosphatase and Tensin Homolog (PTEN) Deficient Tumors: Building PI3Kβ Potency in a PI3Kδ-Selective Template by Targeting Nonconserved Asp856

Autor:	Jerry Evarts, Gary Phillips, Joshua Kaplan, David Koditek, Kathleen S. Keegan, Adam Kashishian, Zhi-Hua Cui, Joseph Therrien, Jennifer Treiberg, Bart Phillips, Latesh Lad, Eve-Irene Lepist, Jayaraman Chandrasekhar, Leena Patel, Anella Yahiaoui, Stephane Perreault, Jia Hao, Mary E. McGrath, Thomas Kenney
Rok vydání:	2017
Předmět:	0301 basic medicine Male Models Molecular Phosphatase Rats Sprague-Dawley 03 medical and health sciences Mice 0302 clinical medicine Dogs In vivo Cell Line Tumor Drug Discovery LNCaP Tensin PTEN Animals Humans Protein Kinase Inhibitors PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors Phosphoinositide 3-kinase biology Chemistry PTEN Phosphohydrolase Prostate Prostatic Neoplasms Haplorhini Molecular biology Rats Class Ia Phosphatidylinositol 3-Kinase 030104 developmental biology 030220 oncology & carcinogenesis Cancer cell biology.protein Cancer research Molecular Medicine
Zdroj:	Journal of medicinal chemistry. 60(4)
ISSN:	1520-4804
Popis:	Phosphoinositide 3-kinase (PI3K) β signaling is required to sustain cancer cell growth in which the tumor suppressor phosphatase and tensin homolog (PTEN) has been deactivated. This manuscript describes the discovery, optimization, and in vivo evaluation of a novel series of PI3Kβ/δ inhibitors in which PI3Kβ potency was built in a PI3Kδ-selective template. This work led to the discovery of a highly selective PI3Kβ/δ inhibitor displaying excellent pharmacokinetic profile and efficacy in a human PTEN-deficient LNCaP prostate carcinoma xenograft tumor model.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::12a2121eb475207997996dbaba211945 https://pubmed.ncbi.nlm.nih.gov/28106991 Zobrazit plný text záznamu