BAY-293

BAY-293
Clinical data
Drug class	SOS1 inhibitor
Identifiers
	IUPAC name 6,7-dimethoxy-2-methyl-N-[(1R)-1-[4-[2-(methylaminomethyl)phenyl]thiophen-2-yl]ethyl]quinazolin-4-amine;
CAS Number	2244904-70-7;
PubChem CID	137322663;
IUPHAR/BPS	10480;
ChemSpider	72380155;
ChEBI	CHEBI:232851;
ChEMBL	ChEMBL4535474;
PDB ligand	AXH (PDBe, RCSB PDB);
Chemical and physical data
Formula	C25H28N4O2S
Molar mass	448.59 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=NC2=CC(=C(C=C2C(=N1)N[C@H](C)C3=CC(=CS3)C4=CC=CC=C4CNC)OC)OC;
	InChI InChI=1S/C25H28N4O2S/c1-15(24-10-18(14-32-24)19-9-7-6-8-17(19)13-26-3)27-25-20-11-22(30-4)23(31-5)12-21(20)28-16(2)29-25/h6-12,14-15,26H,13H2,1-5H3,(H,27,28,29)/t15-/m1/s1; Key:WEGLOYDTDILXDA-OAHLLOKOSA-N;

BAY-293 is the first drug reported to act as an inhibitor of the guanine nucleotide exchange factor protein SOS1. It acts by preventing SOS1 from binding to its target protein KRAS. It has potential applications in the treatment of cancer, and has been widely used in cancer research.^[1]^[2]^[3]^[4]^[5]

References

^ Hillig RC, Sautier B, Schroeder J, Moosmayer D, Hilpmann A, Stegmann CM, et al. (February 2019). "Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS-SOS1 interaction". Proceedings of the National Academy of Sciences of the United States of America. 116 (7): 2551–2560. Bibcode:2019PNAS..116.2551H. doi:10.1073/pnas.1812963116. PMC 6377443. PMID 30683722.
^ Wang CX, Wang TT, Zhang KD, Li MY, Shen QC, Lu SY, et al. (October 2022). "Pan-KRAS inhibitors suppress proliferation through feedback regulation in pancreatic ductal adenocarcinoma". Acta Pharmacologica Sinica. 43 (10): 2696–2708. doi:10.1038/s41401-022-00897-4. PMC 9525295. PMID 35352018.
^ Hamilton G, Stickler S, Rath B (2023). "Integration of signaling pathway and bromodomain and extra-terminal domain inhibition for the treatment of mutant Kirsten rat sarcoma viral oncogene homolog cancer". Exploration of Targeted Anti-Tumor Therapy. 4 (5): 1027–1038. doi:10.37349/etat.2023.00178. PMC 10651355. PMID 38023987.
^ Bruggemann L, Falls Z, Mangione W, Schwartz SA, Battaglia S, Aalinkeel R, et al. (January 2023). "Multiscale Analysis and Validation of Effective Drug Combinations Targeting Driver KRAS Mutations in Non-Small Cell Lung Cancer". International Journal of Molecular Sciences. 24 (2): 997. doi:10.3390/ijms24020997. PMC 9867122. PMID 36674513.
^ Mannino D, Basilotta R, De Luca F, Casili G, Esposito E, Paterniti I (March 2025). "KRAS-SOS-1 Inhibition as New Pharmacological Target to Counteract Anaplastic Thyroid Carcinoma (ATC)". International Journal of Molecular Sciences. 26 (6): 2579. doi:10.3390/ijms26062579. PMC 11942110. PMID 40141222.

[1] Hillig RC, Sautier B, Schroeder J, Moosmayer D, Hilpmann A, Stegmann CM, et al. (February 2019). "Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS-SOS1 interaction". Proceedings of the National Academy of Sciences of the United States of America. 116 (7): 2551–2560. Bibcode:2019PNAS..116.2551H. doi:10.1073/pnas.1812963116. PMC 6377443. PMID 30683722.

[2] Wang CX, Wang TT, Zhang KD, Li MY, Shen QC, Lu SY, et al. (October 2022). "Pan-KRAS inhibitors suppress proliferation through feedback regulation in pancreatic ductal adenocarcinoma". Acta Pharmacologica Sinica. 43 (10): 2696–2708. doi:10.1038/s41401-022-00897-4. PMC 9525295. PMID 35352018.

[3] Hamilton G, Stickler S, Rath B (2023). "Integration of signaling pathway and bromodomain and extra-terminal domain inhibition for the treatment of mutant Kirsten rat sarcoma viral oncogene homolog cancer". Exploration of Targeted Anti-Tumor Therapy. 4 (5): 1027–1038. doi:10.37349/etat.2023.00178. PMC 10651355. PMID 38023987.

[4] Bruggemann L, Falls Z, Mangione W, Schwartz SA, Battaglia S, Aalinkeel R, et al. (January 2023). "Multiscale Analysis and Validation of Effective Drug Combinations Targeting Driver KRAS Mutations in Non-Small Cell Lung Cancer". International Journal of Molecular Sciences. 24 (2): 997. doi:10.3390/ijms24020997. PMC 9867122. PMID 36674513.

[5] Mannino D, Basilotta R, De Luca F, Casili G, Esposito E, Paterniti I (March 2025). "KRAS-SOS-1 Inhibition as New Pharmacological Target to Counteract Anaplastic Thyroid Carcinoma (ATC)". International Journal of Molecular Sciences. 26 (6): 2579. doi:10.3390/ijms26062579. PMC 11942110. PMID 40141222.

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See also

References