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Gene and Protein Information ![]() |
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Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 1333 | 2p22.1 | SOS1 | SOS Ras/Rac guanine nucleotide exchange factor 1 | |
Mouse | - | 1319 | 17 50.67 cM | Sos1 | SOS Ras/Rac guanine nucleotide exchange factor 1 | |
Rat | - | 1319 | 6q11 | Sos1 | SOS Ras/Rac guanine nucleotide exchange factor 1 |
Previous and Unofficial Names ![]() |
GF1 | gingival fibromatosis, hereditary, 1 (GINGF) | HGF | son of sevenless homolog 1 (Drosophila) | SOS-1 |
Database Links ![]() |
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Alphafold | Q07889 (Hs), Q62245 (Mm) |
ChEMBL Target | CHEMBL2079846 (Hs), CHEMBL4523334 (Mm) |
Ensembl Gene | ENSG00000115904 (Hs), ENSMUSG00000024241 (Mm), ENSRNOG00000007106 (Rn) |
Entrez Gene | 6654 (Hs), 20662 (Mm), 313845 (Rn) |
Human Protein Atlas | ENSG00000115904 (Hs) |
KEGG Gene | hsa:6654 (Hs), mmu:20662 (Mm), rno:313845 (Rn) |
OMIM | 182530 (Hs) |
Pharos | Q07889 (Hs) |
RefSeq Nucleotide | NM_005633 (Hs), NM_009231 (Mm), NM_001100716 (Rn) |
RefSeq Protein | NP_005624 (Hs), NP_033257 (Mm), NP_001094186 (Rn) |
UniProtKB | Q07889 (Hs), Q62245 (Mm) |
Wikipedia | SOS1 (Hs) |
Selected 3D Structures ![]() |
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Download all structure-activity data for this target as a CSV file
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Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||
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Other Binding Ligands | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Immuno Process Associations | ||
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General Comments |
SOS1 is a guanine nucleotide exchange factor that regulates the activation state of RAS GTPases. When the RAS/SOS1 complex forms RAS can reload with GTP and is activated. Inhibition of RAS/SOS1 formation prevents reloading with GTP and blocks RAS pathway activation. Blocking the RAS/SOS1 interaction using small-molecules is being explored as a novel antiproliferative mechanism for cancer therapy [1-2,6-7]. This mechanism is operational irrespective of the KRAS alleles present in targeted tumours (including the most common G12D/V/C and G13D oncoproteins). |
1. Burns MC, Howes JE, Sun Q, Little AJ, Camper DV, Abbott JR, Phan J, Lee T, Waterson AG, Rossanese OW et al.. (2018) High-throughput screening identifies small molecules that bind to the RAS:SOS:RAS complex and perturb RAS signaling. Anal Biochem, 548: 44-52. [PMID:29444450]
2. Hillig RC, Sautier B, Schroeder J, Moosmayer D, Hilpmann A, Stegmann CM, Werbeck ND, Briem H, Boemer U, Weiske J et al.. (2019) Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS-SOS1 interaction. Proc Natl Acad Sci USA, 116 (7): 2551-2560. [PMID:30683722]
3. Hodges TR, Abbott JR, Little AJ, Sarkar D, Salovich JM, Howes JE, Akan DT, Sai J, Arnold AL, Browning C et al.. (2018) Discovery and Structure-Based Optimization of Benzimidazole-Derived Activators of SOS1-Mediated Nucleotide Exchange on RAS. J Med Chem, 61 (19): 8875-8894. [PMID:30205005]
4. Hofmann MH, Gmachl M, Ramharter J, Savarese F, Gerlach D, Marszalek JR, Sanderson MP, Kessler D, Trapani F, Arnhof H et al.. (2021) BI-3406, a Potent and Selective SOS1-KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition. Cancer Discov, 11 (1): 142-157. [PMID:32816843]
5. Ketcham JM, Haling J, Khare S, Bowcut V, Briere DM, Burns AC, Gunn RJ, Ivetac A, Kuehler J, Kulyk S et al.. (2022) Design and Discovery of MRTX0902, a Potent, Selective, Brain-Penetrant, and Orally Bioavailable Inhibitor of the SOS1:KRAS Protein-Protein Interaction. J Med Chem, 65 (14): 9678-9690. [PMID:35833726]
6. Lu S, Jang H, Zhang J, Nussinov R. (2016) Inhibitors of Ras-SOS Interactions. ChemMedChem, 11 (8): 814-21. [PMID:26630662]
7. Winter JJ, Anderson M, Blades K, Brassington C, Breeze AL, Chresta C, Embrey K, Fairley G, Faulder P, Finlay MR et al.. (2015) Small molecule binding sites on the Ras:SOS complex can be exploited for inhibition of Ras activation. J Med Chem, 58 (5): 2265-74. [PMID:25695162]
8. Zhang S, Zhang Y, Chen X, Xu J, Fang H, Li Y, Liu Y, He H. (2022) Design and Structural Optimization of Orally Bioavailable SOS1 Inhibitors for the Treatment of KRAS-Driven Carcinoma. J Med Chem, 65 (23): 15856-15877. [PMID:36384290]
Rho GEFs: SOS Ras/Rac guanine nucleotide exchange factor 1. Last modified on 21/11/2022. Accessed on 18/03/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3096.