Inhibitory activities

DMH1, a small molecule inhibitor of BMP Type I receptors, potently reduced lung cell proliferation, promoted cell death, and decreased cell migration and invasion in NSCLC cells by blocking BMP signaling, It suppressed Smad 1/5/8 phosphorylation and gene expression of Id1, Id2 and Id3.

Cell lines

A549 and H460 cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

Cell scratch-wound Assay: 24 h DMH1 at 1 μM and 3μM concentrations. Cell Proliferation Assay：incubated for 48 hours and 96 hours

Applications

DMH1 blocked BMP signaling in NSCLC cells and decreased NSCLC cell migration and invasion, DMH1 reduces NSCLC cell proliferation and induces cell death

Animal models

Xenograft model

Dosage form

5 mg/kg DMH1 every other day.

Preparation method

dissolved in 12.5% 2-hydroxypropyl-b-cyclodextrin

Application

The rate for doubling tumor size in DMH1-treated mice was about one day longer than the controls (5.6 versus 4.7 days in the DMH1 treated and control mice, respectively). MH1 treatment resulted in a statistically significant reduction in tumor volumes by about 50% compared to the vehicle control group. In a word , DMH1 attenuated xenograft lung tumor growth in mice

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

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.