VUBI1

Activity is in the single digit µM range. However, cellular concentration ranges higher than 10 µM are not recommended due to the absence of selectivity data of any kind.

VUBI1 is the most potent SOS1 activator with a confirmed biophysical interactions to SOS1 in a RAS:SOS1:RAS co-crystal structure. VUBI1 demonstrated the typical biphasic modulation of downstream pERK1/2 on T202/Y204, but despite it's biochemical Kd of 44 nM, the cellular activity is only mediocre (EC50 ~6 µM). Although the Pharmacological data in the described In-Cell Western are supporting the proposed MoA, the weak cellular activity in combination with a lack of selectivity data is a general concern. As additional tools, the regioisomeric negative control (BI-9930) or SOS1 inhibitors with the opposite pharmacology like BAY-293 or BI-3406 might be considered.