Kirsten rat sarcoma virus oncogene homolog (KRAS) - Son of Sevenless homolog 1 (SOS1) protein-protein interface (KRAS-SOS1 interface)

The Kirsten rat sarcoma virus oncogene homolog (KRAS) - Son of Sevenless homolog 1 (SOS1) protein-protein interface is a critical regulatory node in the RAS/MAPK signaling pathway (UniProt: P01116, Q07889). KRAS functions as a molecular switch that cycles between an inactive GDP-bound state and an active GTP-bound state. SOS1, a guanine nucleotide exchange factor (GEF), facilitates the activation of KRAS by promoting the dissociation of GDP, allowing GTP to bind (PMID: 33067308). In many cancers, KRAS is constitutively active due to mutations, driving uncontrolled cell proliferation and survival. Targeting the KRAS-SOS1 interface with small molecules prevents this nucleotide exchange, effectively locking KRAS in its inactive state regardless of the specific mutation present. This strategy aims to inhibit downstream oncogenic signaling and is currently being explored in clinical trials for various KRAS-driven malignancies (ClinicalTrials.gov: NCT04111458).

Other names

KRAS-SOS1 interactionKRAS:SOS1 complexSOS1-KRAS interfaceRAS-SOS interface

Inhibition of the protein-protein interaction between KRAS and SOS1, preventing the SOS1-mediated exchange of GDP for GTP on KRAS, thereby maintaining KRAS in an inactive state (PMID: 31439706).