SOS1 (395)

SOS1 (Son of sevenless homolog 1) is a guanine nucleotide exchange factor (GEF) responsible for facilitating the exchange of GDP for GTP, thereby activating RAS proteins. SOS1 contains two binding sites for RAS-family proteins: a catalytic site that interacts with GDP-bound RAS-family proteins to promote guanine nucleotide exchange, and an allosteric site that binds GTP-bound RAS-family proteins, further enhancing SOS1's catalytic GEF activity. Upon stimulation by growth factors, SOS-Grb2 complexes associate with activated receptors, enabling the activation of Ras through the membrane localization of SOS and Ras. Small molecule inhibitors targeting SOS1 have demonstrated efficacy in reducing active RAS levels in tumor cells with either wild-type KRAS or KRAS mutations. By disrupting the KRAS-SOS1 interaction, these inhibitors prevent the reloading of KRAS with GTP, resulting in antiproliferative effects.