VUBI1

VUBI1 ( SOS1 activator 1) is a benzimidazole derivative and SOS1 activator with a K d of 44 nM. VUBI1 can significantly activate RAS-GTP and regulate the phosphorylation of ERK. VUBI1 also can serve as a target ligand for synthesizing PROTACs, such as PROTAC SOS1 degrader-1, to induce SOS1 degradation. VUBI1 can be used in the study of cancer ^{[1] [2] [3] [4]}.

In Vitro, VUBI1 (Compound 64) (0.3-30 µM; 10 min) increases RAS-GTP levels and biphasically modulates ERK1/2 phosphorylation in HeLa cells (inducing peak levels at low concentrations and suppressing at high concentrations)^[1].

References:
[1]. Timothy R Hodges, et al. Discovery and Structure-Based Optimization of Benzimidazole-Derived Activators of SOS1-Mediated Nucleotide Exchange on RAS. J Med Chem. 2018 Oct 11;61(19):8875-8894.
[2]. Zhou C, et al. Discovery of the First-in-Class Agonist-Based SOS1 PROTACs Effective in Human Cancer Cells Harboring Various KRAS Mutations. J Med Chem. 2022 Mar 10;65(5):3923-3942.
[3]. Stickler S, et al. Targeting KRAS in pancreatic cancer. Oncol Res. 2024 Apr 23;32(5):799-805.
[4]. Hamilton G, et al. Targeting of SOS1: from SOS1 Activators to Proteolysis Targeting Chimeras. Curr Pharm Des. 2023;29(22):1741-1746.