Ask about this productRelated genes to: SOS1 antibody
- Gene:
- SOS1 NIH gene
- Name:
- SOS Ras/Rac guanine nucleotide exchange factor 1
- Previous symbol:
- GINGF
- Synonyms:
- HGF, GF1
- Chromosome:
- 2p22.1
- Locus Type:
- gene with protein product
- Date approved:
- 1993-10-27
- Date modifiied:
- 2019-04-23
Related products to: SOS1 antibody
Related articles to: SOS1 antibody
- Oncogenic KRAS signaling is among the most prevalent drivers in human cancer, yet durable pathway suppression has historically been limited by incomplete target coverage, toxicity constraints for downstream kinase inhibitors, and rapid adaptive rewiring through receptor tyrosine kinase (RTK) feedback. A renewed focus on the KRAS activation cycle has positioned SOS1-an RTK-coupled guanine nucleotide exchange factor-as an attractive upstream node to modulate KRAS output across multiple alleles. By disrupting the KRAS-SOS1 protein-protein interaction (PPI) or otherwise limiting SOS1-mediated nucleotide exchange, SOS1-directed agents reduce RAS-GTP formation and suppress Mitogen-Activated Protein Kinase (MAPK) signaling, while also attenuating feedback-driven rebound that commonly follows MEK/ERK inhibition or allele-specific KRAS targeting. In this review, we summarize the structural and mechanistic basis of RAS-SOS engagement, the emergence of a druggable pocket on SOS1 exploited by modern inhibitors, and the evolution from peptide/interface-mimic approaches to potent small-molecule PPI disruptors. We synthesize key pharmacology across tool compounds and clinical candidates, emphasizing biomarker-linked pharmacodynamic readouts (RAS-GTP and Phosphorylated extracellular signal-regulated kinase (pERK)), context dependence (KRAS allele, RTK tone, and pathway baseline), and on-target validation strategies spanning biophysics, structural biology, and cellular engagement. We then discuss why SOS1 inhibitors act as "multiplier" drugs in rational combinations-particularly with MEK inhibitors and KRAS (G12C) inhibitors-outline expected resistance routes and candidate predictive biomarkers, and review the current clinical landscape for SOS1 inhibitors and combination trial design. Finally, we highlight emerging directions including next-generation, brain-penetrant chemistry and event-driven SOS1 degraders, and propose priorities for translating upstream exchange control into durable patient benefit. - Source: PubMed
Publication date: 2026/04/07
Kamel Emadeldin MKhadrawy Sally MostafaAli Mohamed A MAbukhadra Mostafa RYassin Nour Y SAlkhedhairi SalehAba Alkhayl Faris FLamsabhi Al Mokhtar - Historically, KRAS mutations have been notoriously difficult to target despite their status as the most commonly mutated oncogene in the RAS gene family. However, pioneering work by Shokat and colleagues has led to the discovery of KRAS G12C-GDP mutant specific inhibitors, with two such inhibitors adagrasib and sotorasib now FDA approved for treatment of non-small cell lung cancer (NSCLC). Unfortunately, despite FDA approval, several patients did not achieve full treatment response. Further drug discovery is urgently needed to identify compounds capable of synergizing with available KRAS G12C inhibitors to prevent drug resistance, pan-KRAS inhibitors capable of binding multiple KRAS mutations, and KRAS-GTP inhibitors. - Source: PubMed
Publication date: 2026/04/20
Samudrala RamBruggemann LianaFalls ZackaryMahajan Supriya D - This study aimed to describe the clinical manifestations and genetic variants of Noonan syndrome in a Colombian pediatric population and to identify the genes most frequently associated with specific phenotypic features. - Source: PubMed
Publication date: 2026/04/16
Martínez Rueda Silvia CDel Pilar Montilla MariaBaquero CarolinaGómez SusanaLopera Maria VictoriaZuluaga Nora AlejandraForero Adriana CarolinaGiraldo GustavoPineda Trujillo NicolásMartínez Juan CamiloDurán Ventura PaolaAlfaro Juan Manuel - This study aimed to assess the detection rate and spectrum of pathogenic variants (PVs) and candidate variants (variants of uncertain significance, VUS) in AVM patients. - Source: PubMed
Publication date: 2026/04/16
Schmidt Vanessa FSchanze DennyBrill RichardLoeser Julius HUller WibkeDoppler MichaelCangir ÖzlemHengst SusanneVielsmeier VeronikaPech MaciejObereisenbuchner FlorianSchirren MirjamSint AlenaPuhr-Westerheide DanielDeniz SinanWeiß Jakob B WHäberle BeateHartel AlexandraFröba-Pohl AlexandraHaehl JuliaHolm AnnegretSporns Peter BScherf ThomasRicke JensLassmann SilkeSeidensticker MaxWohlgemuth Walter AKimm Melanie AZenker MartinWildgruber MoritzKapp Friedrich G - By controlling biochemical function and stress-related gene expression, ZnO nano-priming improved barley salinity tolerance beyond hydro-priming, demonstrating its coordinated biochemical and molecular effects. Salinity stress is a significant abiotic constraint that disrupts redox homeostasis and ionic equilibrium of barley. Nano-priming has emerged as an effective tool to mitigate these impacts by improving stress-responsive pathways. To investigate the biochemical and molecular responses to salt stress, 10 contrasting genotypes were selected from 170 genotypes screened under control conditions and at 200 mM NaCl using unprimed, hydro-primed, and nano-primed seeds. Biochemical traits, including protein, carbohydrates, proline, mineral absorption, and antioxidant activity, were assessed. QPCR was used to quantify the expression of 10 stress-related genes (CAT1, APX, SODA, GPX, GR, NHX1, NHX2, NHX3, SOS1, SOS3). Compared to unprimed and hydro-primed seeds, nano-priming significantly increased osmolyte accumulation, mineral absorption, and antioxidant enzyme activity. Principal component analysis and hierarchical clustering confirmed significant genotype-specific responses, with ionic traits (K⁺, K⁺/Na⁺) and antioxidant enzymes (CAT, GST, POD) driving separation under salinity. Under salinity, CAT1 was strongly expressed in the tolerant genotype HOR11370 (79.02-fold), while NHX3 was highly expressed in the tolerant genotype BCC1398 (208.16-fold). Nano-priming also significantly upregulates CAT1 in the sensitive genotype BCC532. These findings provide molecular evidence that nano-priming enhances barley resilience by reprogramming gene expression, ion transport, and antioxidant pathways. The differential regulations within and among tolerant and sensitive genotypes indicate that the integration of multiple mechanisms confers salinity tolerance in barley. These findings provide valuable insights into breeding strategies to improve crop performance under saline conditions. - Source: PubMed
Publication date: 2026/04/13
Abozaid Wesam WThabet Samar GKaram Mohamed AMoursi Yasser S