Characterization of the RAC1/CDC42 inhibitor MBQ-167 to assess its utility as a tool for interrogating RHO GTPase biology

RAC1 and CDC42 are members of the Rho family of small GTPases that promote cell survival, cell cycle progression, proliferation, migration and invasion, therefore play a key role in anchoring independent growth, cell transformation and metastasis. Targeting RAC proteins and CDC42 holds great anti-tumoral potential. We used the Simulated Cell to perform in silico KO of CDC42 and RAC1 in a panel of 911 cancer cell line avatars. The results showed that the ability of RAC1 to reduce viability was broader than that of CDC42 (a higher number of cell line avatars died upon RAC1 KO than upon CDC42 KO), revealing a difference in essentiality not previously exposed by a reference public in vitro dataset (DepMap).