Malolactone strikes: K-Ras-G12D's Achilles' heel.
K-Ras-G12D
alkylation
covalent inhibitor
malolactone
strain release
Journal
Trends in pharmacological sciences
ISSN: 1873-3735
Titre abrégé: Trends Pharmacol Sci
Pays: England
ID NLM: 7906158
Informations de publication
Date de publication:
22 Apr 2024
22 Apr 2024
Historique:
received:
01
04
2024
revised:
06
04
2024
accepted:
07
04
2024
medline:
24
4
2024
pubmed:
24
4
2024
entrez:
23
4
2024
Statut:
aheadofprint
Résumé
In a recent study in Nature Chemical Biology, Zheng et al. exploiting strain release by malolactone-based electrophiles and designed a first-in-class covalent inhibitor that targets the elusive aspartate of the Kirsten rat sarcoma viral oncogene homolog (K-Ras)-G12D variant, which is highly prevalent in pancreatic cancer. The compound drastically inhibited oncogenic signaling and tumor growth in preclinical K-Ras-G12D-mutant pancreatic cancer models, expanding treatment potential beyond K-Ras-G12C-targeted therapies.
Identifiants
pubmed: 38653668
pii: S0165-6147(24)00066-X
doi: 10.1016/j.tips.2024.04.001
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no conflict of interest.