DMH1 is a small molecule inhibitor of bone morphogenetic protein (BMP) signaling with IC50 value of 107.9nM against ALK2 [1].
DMH1 is an analog of dorsomorphin. It exclusively targets BMP and has no effect on VEGF signaling. DMH1 shows potent and specific inhibitory activity against purified human BMP type-I receptor ALK2 with IC50 value of 107.9nM. It shows no significant inhibition of purified KDR, ALK5, AMPK and PDGFRβ. In cells respectively transfected with the active forms of ALK2, ALK3 and ALK6, DMH1 effectively inhibits signaling by ALK2 and ALK3 with IC50 values of both less than 0.5μM. In addition, DMH1 has no effect on the p38/MAP kinase signaling or the Activin A-induced Smad2 activation [1].
Moreover, DMH1 is found to have antitumor effect in lung cancer through blocking BMP signaling. In the NSCLC cell line A549 cells, DMH1 inhibits the phosphorylation of Smad 1/5/8 and decreases the expression of Id1, Id2 and Id3 genes. It decreases cell migration and invasion in A549 and H460 cell line. Besides that, DMH1 reduces cell proliferation and induces cell death in A549 cells. In the A549 tumor xenograft in mice, treatment of DMH1significantly suppresses tumor growth [2].
References:
[1] Hao J, Ho J N, Lewis J A, et al. In vivo structure- activity relationship study of dorsomorphin analogues identifies selective VEGF and BMP inhibitors. ACS chemical biology, 2010, 5(2): 245-253.
[2] Hao J, Lee R, Chang A, et al. DMH1, a Small Molecule Inhibitor of BMP Type I Receptors, Suppresses Growth and Invasion of Lung Cancer. PloS one, 2014, 9(3): e90748.