Hexachlorophene, a selective SHP2 inhibitor, suppresses proliferation and metastasis of KRAS-mutant NSCLC cells by inhibiting RAS/MEK/ERK and PI3K/AKT signaling pathways.
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Cell Line, Tumor
Cell Proliferation
Hexachlorophene
Humans
Lung Neoplasms
/ drug therapy
Mitogen-Activated Protein Kinase Kinases
/ metabolism
Molecular Docking Simulation
Mutation
Phosphatidylinositol 3-Kinases
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Proto-Oncogene Proteins p21(ras)
/ genetics
Signal Transduction
Hexachlorophene
Inhibitor
Non-small cell lung cancer
RAS
SHP2
Journal
Toxicology and applied pharmacology
ISSN: 1096-0333
Titre abrégé: Toxicol Appl Pharmacol
Pays: United States
ID NLM: 0416575
Informations de publication
Date de publication:
15 04 2022
15 04 2022
Historique:
received:
10
12
2021
revised:
04
03
2022
accepted:
14
03
2022
pubmed:
22
3
2022
medline:
30
4
2022
entrez:
21
3
2022
Statut:
ppublish
Résumé
Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations account for 35% of the genetic alterations in non-small cell lung cancer (NSCLC). The Src-homology region 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, is closely involved in RAS downstream pathways and development of many tumors by affecting cell proliferation, differentiation, and immunity. Targeting SHP2 with small molecules may be a promising avenue for the treatment of KRAS-mutant (mut) NSCLC. Herein, hexachlorophene (HCP) was identified as a SHP2 inhibitor with an IC
Identifiants
pubmed: 35307375
pii: S0041-008X(22)00133-8
doi: 10.1016/j.taap.2022.115988
pii:
doi:
Substances chimiques
KRAS protein, human
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Mitogen-Activated Protein Kinase Kinases
EC 2.7.12.2
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Hexachlorophene
IWW5FV6NK2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
115988Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.