QSAR of clinically important EGFR mutant L858R/T790M pyridinylimidazole inhibitors.
EGFR
QSAR
T790M
Williams plot
double mutant inhibitor
irreversible inhibitors
Journal
Chemical biology & drug design
ISSN: 1747-0285
Titre abrégé: Chem Biol Drug Des
Pays: England
ID NLM: 101262549
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
04
06
2018
revised:
05
01
2019
accepted:
31
01
2019
pubmed:
28
2
2019
medline:
25
8
2020
entrez:
28
2
2019
Statut:
ppublish
Résumé
EGFR is a well-established therapeutic target of clinical relevance in cancer. However, acquisition of secondary mutation (T790M) makes first-generation inhibitors ineffective. Therefore, to circumvent the problem of resistance, new T790M/L858R (TMLR) double mutant inhibitors are required. In this study, fragment-based QSAR models (GQSAR) were generated for pyridinylimidazole derivatives having biological activity against TMLR mutants. The GQSAR model developed using partial least squares regression via stepwise forward-backward variable selection technique showed best results as judged using statistical parameters (r
Substances chimiques
Imidazoles
0
Protein Kinase Inhibitors
0
Pyridines
0
ErbB Receptors
EC 2.7.10.1
pyridine
NH9L3PP67S
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1306-1315Informations de copyright
© 2019 John Wiley & Sons A/S.