Structure-Based Drug Design and Synthesis of PI3Kα-Selective Inhibitor (PF-06843195).
Animals
Cell Line
Chromatography, High Pressure Liquid
/ methods
Crystallography, X-Ray
Drug Design
Humans
Hydrogen Bonding
Magnetic Resonance Spectroscopy
/ methods
Mice
Molecular Structure
Phosphatidylinositol 3-Kinases
/ drug effects
Phosphoinositide-3 Kinase Inhibitors
/ chemical synthesis
Rats
Spectrometry, Mass, Electrospray Ionization
/ methods
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
14 01 2021
14 01 2021
Historique:
pubmed:
29
12
2020
medline:
9
3
2021
entrez:
28
12
2020
Statut:
ppublish
Résumé
The phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway is a frequently dysregulated pathway in human cancer, and PI3Kα is one of the most frequently mutated kinases in human cancer. A PI3Kα-selective inhibitor may provide the opportunity to spare patients the side effects associated with broader inhibition of the class I PI3K family. Here, we describe our efforts to discover a PI3Kα-selective inhibitor by applying structure-based drug design (SBDD) and computational analysis. A novel series of compounds, exemplified by 2,2-difluoroethyl (3
Identifiants
pubmed: 33356246
doi: 10.1021/acs.jmedchem.0c01652
doi:
Substances chimiques
Phosphoinositide-3 Kinase Inhibitors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM