Effects of Single Nucleotide Polymorphisms on the Binding of Afatinib to EGFR: A Potential Patient Stratification Factor Revealed by Modeling Studies.
Journal
Journal of chemical information and modeling
ISSN: 1549-960X
Titre abrégé: J Chem Inf Model
Pays: United States
ID NLM: 101230060
Informations de publication
Date de publication:
28 01 2019
28 01 2019
Historique:
pubmed:
28
11
2018
medline:
4
12
2019
entrez:
28
11
2018
Statut:
ppublish
Résumé
The anticancer drug afatinib has been found to be more effective at inhibiting the oncogenic EGFR mutant exon 19 deletion (19del) over the oncogenic EGFR mutant L858R. The underlying mechanism has been hypothesized to result from differences in structural constraints introduced by the mutations and stabilizing interactions afforded by a buried water molecule in 19del (Kannan, S.; et al. Sci. Rep. 2017, 7, 1540). The COSMIC cancer database is mined for EGFR sequences to discover that several mutations in the form of Single nucleotide polymorphisms (SNPs) line this hydration cavity. In this work, the effects of these SNPs on the affinity of afatinib for EGFR
Identifiants
pubmed: 30481018
doi: 10.1021/acs.jcim.8b00491
doi:
Substances chimiques
Afatinib
41UD74L59M
ErbB Receptors
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM