VUBI1

VUBI1
Clinical data
Drug class	SOS1 activator
Identifiers
	IUPAC name 6-chloro-2-(2,6-diazaspiro[3.3]heptan-2-yl)-1-[(4-fluoro-3,5-dimethylphenyl)methyl]-4-(4-methylpiperazin-1-yl)benzimidazole;
CAS Number	2245237-53-8;
PubChem CID	134814234;
Chemical and physical data
Formula	C26H32ClFN6
Molar mass	483.03 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=CC(=CC(=C1F)C)CN2C3=C(C(=CC(=C3)Cl)N4CCN(CC4)C)N=C2N5CC6(C5)CNC6;
	InChI InChI=1S/C26H32ClFN6/c1-17-8-19(9-18(2)23(17)28)12-34-22-11-20(27)10-21(32-6-4-31(3)5-7-32)24(22)30-25(34)33-15-26(16-33)13-29-14-26/h8-11,29H,4-7,12-16H2,1-3H3; Key:JWZAQUXBYYOGFA-UHFFFAOYSA-N;

VUBI1 is a drug that acts as an activator of the guanine nucleotide exchange factor protein SOS1, increasing the rate at which it catalyzes the exchange of GDP for GTP on its target protein KRAS. While inhibitors of SOS1 have been more widely researched for the treatment of cancer, under some conditions increasing SOS1 activity can also have an anti-cancer effect by destructive overactivation of cellular signaling processes, so SOS1 activators are also of potential clinical interest, as well as being used for the study of the SOS1-KRAS intercellular pathway.^[1]^[2]

References

^ Hodges TR, Abbott JR, Little AJ, Sarkar D, Salovich JM, Howes JE, et al. (October 2018). "Discovery and Structure-Based Optimization of Benzimidazole-Derived Activators of SOS1-Mediated Nucleotide Exchange on RAS". Journal of Medicinal Chemistry. 61 (19): 8875–8894. doi:10.1021/acs.jmedchem.8b01108. PMC 8314423. PMID 30205005.
^ Hamilton G, Stickler S, Rath B (2023). "Targeting of SOS1: from SOS1 Activators to Proteolysis Targeting Chimeras". Current Pharmaceutical Design. 29 (22): 1741–1746. doi:10.2174/1381612829666230418114520. PMID 37073657.

[1] Hodges TR, Abbott JR, Little AJ, Sarkar D, Salovich JM, Howes JE, et al. (October 2018). "Discovery and Structure-Based Optimization of Benzimidazole-Derived Activators of SOS1-Mediated Nucleotide Exchange on RAS". Journal of Medicinal Chemistry. 61 (19): 8875–8894. doi:10.1021/acs.jmedchem.8b01108. PMC 8314423. PMID 30205005.

[2] Hamilton G, Stickler S, Rath B (2023). "Targeting of SOS1: from SOS1 Activators to Proteolysis Targeting Chimeras". Current Pharmaceutical Design. 29 (22): 1741–1746. doi:10.2174/1381612829666230418114520. PMID 37073657.

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