SOS1 allosteric inhibitor

SOS1 allosteric inhibitors are a class of small molecules designed to target the allosteric binding site of the Son of Sevenless homolog 1 (SOS1) protein. SOS1 is a guanine nucleotide exchange factor (GEF) that activates Ras proteins by facilitating the exchange of GDP for GTP. While catalytic site inhibitors target the primary interaction between SOS1 and inactive Ras, allosteric inhibitors block a secondary site where active Ras binds to create a "feed-forward" activation loop. By disrupting this loop, these inhibitors selectively suppress the hyperactivation of wild-type Ras (H/N/Kras) that is required for oncogenic KRAS-driven tumorigenesis. Research presented by Cincinnati Children's Hospital Medical Center indicates that these inhibitors may offer superior selectivity for KRAS-mutant cells, such as those in pancreatic cancer, compared to catalytic inhibitors, potentially reducing toxicity to normal cells.

Other names

SOS1 allosteric inhibitorsSOS-1 allosteric inhibitorsSOS 1 allosteric inhibitors