Efficacy of inhibitor on wild-type ACVR1 and R206H mutant in C2C12 cells (by DLA)

There are concerns that compounds that are effective in inhibiting ALK2 by occupying its ATP-binding pocket might have reduced efficacy against mutant ALK2. That will be undesirable since the compounds should also target the mutant gain-of-function ALK2 in DIPG cells. The following experiment takes advantage of the fact that ALK2-R206H mutant confers a neofunction of being activated by Activin A (not activating towards wild-type ALK2). Therefore, using Activin A as the stimulation ligand, the effectiveness of inhibition on ALK2-R206H can be specifically determined. BMP6 which activates both wild-type ALK2 and ALK2-R206H is also included.