M4K2234 is a potent, selective ALK1 (ACVRL1) and ALK2 (ACVR1) protein kinase inhibitor with IC50 of 7 and 14 nM, respectively.
M4K2234 inhibits only ALK1/2 and one additional off target (TNIK) by kinome-wide screening against 375 protein kinases at 1 uM.
M4K2234 demonstrated in cell based target engagement assays with an IC50 of 83nM for ALK1 and 13 nM for ALK2.
M4K2234 exhibits only very weak potency against ALK4/5.
M4K2234 affects phosphorylation of SMAD1/5/8 that corresponds to BMP branch of signalling which is mediated, besides others, also by ALK1/2 kinases.
M4K2234 has only a very weak effect on SMAD2/3 phosphorylation that corresponds to TGF beta branch of signalling which is mediated mostly via ALK4/5/7.
