One Atom Makes All the Difference: Getting a Foot in the Door between SOS1 and KRAS.
Afatinib
/ chemistry
Allosteric Regulation
/ drug effects
Binding Sites
Catalytic Domain
Colorectal Neoplasms
/ drug therapy
ErbB Receptors
/ antagonists & inhibitors
Humans
Molecular Dynamics Simulation
Mutagenesis, Site-Directed
Protein Interaction Maps
/ drug effects
Proto-Oncogene Proteins p21(ras)
/ antagonists & inhibitors
Quinazolines
/ chemistry
SOS1 Protein
/ agonists
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:
27 05 2021
27 05 2021
Historique:
pubmed:
16
3
2021
medline:
22
6
2021
entrez:
15
3
2021
Statut:
ppublish
Résumé
KRAS, the most common oncogenic driver in human cancers, is controlled and signals primarily through protein-protein interactions (PPIs). The interaction between KRAS and SOS1, crucial for the activation of KRAS, is a typical, challenging PPI with a large contact surface area and high affinity. Here, we report that the addition of only one atom placed between Y884
Identifiants
pubmed: 33719426
doi: 10.1021/acs.jmedchem.0c01949
doi:
Substances chimiques
KRAS protein, human
0
Quinazolines
0
SOS1 Protein
0
quinazolin-4-amine
0
Afatinib
41UD74L59M
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM