Stemolecule Dorsomorphin dihydrochloride (also known as Compound C) is a potent inhibitor of AMP-activated protein kinase (AMPK) (Ki=109 nM) and bone morphogenic protein (BMP) signaling1,2. It was identified in a screen for compounds that perturb dorsoventral axis formation in zebrafish3. Dorsomorphin functions through inhibition of BMP type I receptors ALK2, ALK3 and ALK6 and thus blocks BMP-mediated SMAD1/5/8 phosphorylation3. BMP signaling coordinates developmental patterning and have essential physiological roles in mature organisms4,5. Dorsomorphin has been used to probe BMP signaling in iron-hepcidin homeostasis, cardiomyogenesis and osteogenesis3,6,7.
Gao, Y., Zhou, Y., Xu, A., and Wu, D. (2008) Effects of an AMP-activated protein kinase inhibitor, compound C, on adipogenic differentiation of 3T3-L1 cells. Biol Pharm Bull 31: 1716-1722.
Anderson, G.J., and Darshan, D. (2008) Small-molecule dissection of BMP signaling. Nat Chem Biol 4: 15-16.
Yu, P.B., Hong, C.C., Sachidanandan, C., Babitt, J.L., Deng, D.Y., Hoyng, S.A., Lin, H.Y., Bloch, K.D., and Peterson, R.T. (2008) Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol 4: 33-41.
Heisenberg, C.P., and Solnica-Krezel, L. (2008) Back and forth between cell fate specification and movement during vertebrate gastrulation. Curr Opin Genet Dev 18: 311-316.
Cain, J.E., Hartwig, S., Bertram, J.F., and Rosenblum, N.D. (2008) Bone morphogenetic protein signaling in the developing kidney: present and future. Differentiation 76: 831-842.
Hao, J., Daleo, M.A., Murphy, C.K., Yu, P.B., Ho, J.N., Hu, J., Peterson, R.T., Hatzopoulos, A.K., and Hong, C.C. (2008) Dorsomorphin, a selective small molecule inhibitor of BMP signaling, promotes cardiomyogenesis in embryonic stem cells. PLoS One 3: e2904.
Seib, F.P., Franke, M., Jing, D., Werner, C., and Bornhauser, M. (2009) Endogenous bone morphogenetic proteins in human bone marrow-derived multipotent mesenchymal stromal cells. Eur J Cell Biol 88: 257-271.
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