Discovery of a Bicyclic Peptidyl Pan-Ras Inhibitor.
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:
09 09 2021
09 09 2021
Historique:
pubmed:
21
8
2021
medline:
15
12
2021
entrez:
20
8
2021
Statut:
ppublish
Résumé
The Ras subfamily of small GTPases is mutated in ∼30% of human cancers and represents compelling yet challenging anticancer drug targets owing to their flat protein surface. We previously reported a bicyclic peptidyl inhibitor, cyclorasin B3, which binds selectively to Ras-GTP with modest affinity and blocks its interaction with downstream effector proteins in vitro but lacks cell permeability or biological activity. In this study, optimization of B3 yielded a potent pan-Ras inhibitor, cyclorasin B4-27, which binds selectively to the GTP-bound forms of wild-type and mutant Ras isoforms (
Identifiants
pubmed: 34415745
doi: 10.1021/acs.jmedchem.1c01130
pmc: PMC8429249
mid: NIHMS1735248
doi:
Substances chimiques
Antineoplastic Agents
0
Peptides, Cyclic
0
Protein Isoforms
0
ras Proteins
EC 3.6.5.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
13038-13053Subventions
Organisme : NCI NIH HHS
ID : P30 CA016058
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA234124
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM122459
Pays : United States
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