Efficacy of inhibitor on wild-type ALK2 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 gain-of-function mutant ALK2 in DIPG cells. The following experiment takes advantage of the fact that Activin A activates ALK2-R206H mutant but not wild-type ALK2.

ALK2-R206H mutant can be inhibited similarly to wild-type ALK2In conclusion, ALK2-R206H mutant is not more resistant to inhibitor LDN193189 compared to wild-type ALK2. For experimental details, please refer to Zenodo.

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