Stemolecule™ Dorsomorphin

Stemolecule Dorsomorphin dihydrochloride (also known as Compound C) is a potent inhibitor of AMP-activated protein kinase (AMPK) (K_i=109nM) and bone morphogenic protein (BMP) signaling^1,2. 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 organisms^4,5. Dorsomorphin has been used to probe BMP signaling in iron-hepcidin homeostasis, cardiomyogenesis and osteogenesis^3,6,7.

Specifications

Product Name: Stemolecule Dorsomorphin

Catalog Number: 04-0024

Size: 2 mg

Alternate Name(s):

• Compound C
• 6-[4-(2-piperidin-1-ylethoxy)phenyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidine

Chemical Formula: C₂₄H₂₅N₅O.₂·HCl·H₂O

Molecular Weight: 490.43

CAS Number: 866405-64-3

Purity: Greater than 99% by HPLC analysis

Formulation: Yellow solid

Solubility: For a 10 mM concentrated stock solution of Dorsomorphin, reconstitute the compound by adding 407.8 µL of DMSO to the entire contents of the vial. If precipitate is observed, warm the solution to 37 °C for 2 to 5 minutes. For cell culture, the media should be prewarmed prior to adding the reconstituted compound. Note: for most cells, the maximum tolerance to DMSO is less than 0.5%. This molecule is soluble in DMSO at 20 mM and water at 100 mM.

Storage and Stability: Store powder at 4 °C protected from light. Information about the stability of Stemolecules in solution is largely not available. As a general guideline, we recommend that stock solution be freshly made and stored in aliquots at −20 °C, protected from light. The effect of storage of stock solutions should be verified for each application.

Quality Control: The purity of Dorsomorphin was determined by HPLC analysis. The accurate mass was determined by mass spectrometry. Cellular toxicity of Dorsomorphin was tested on mouse embryonic stem cells.

Resources

1. Gao, Y., Zhou, Y., Xu, A., and Wu, D. Effects of an AMP-activated protein kinase inhibitor, compound C, on adipogenic differentiation of 3T3-L1 cells. Biol Pharm Bull 31: 1716-1722 (2008).
2. Anderson, G.J., and Darshan, D. Small-molecule dissection of BMP signaling. Nat Chem Biol 4: 15-16 (2008).
3. 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. Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol 4: 33-41 (2008).
4. Heisenberg, C.P., and Solnica-Krezel, L. Back and forth between cell fate specification and movement during vertebrate gastrulation. Curr Opin Genet Dev 18: 311-316 (2008).
5. Cain, J.E., Hartwig, S., Bertram, J.F., and Rosenblum, N.D. Bone morphogenetic protein signaling in the developing kidney: Present and future. Differentiation 76: 831-842 (2008).
6. 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. Dorsomorphin, a selective small molecule inhibitor of BMP signaling, promotes cardiomyogenesis in embryonic stem cells. PLoS One 3: e2904 (2008).
7. Seib, F.P., Franke, M., Jing, D., Werner, C., and Bornhauser, M. Endogenous bone morphogenetic proteins in human bone marrow-derived multipotent mesenchymal stromal cells. Eur J Cell Biol 88: 257-271 (2009).

Additional Publications

• Cheon SH; Culver AM; Bagnell AM; Ritchie FD; Clytus JM; McCord M; Papendorp CM; Chukwurah E; Smith AJ; Cowen MH; Ghate PS; Davis SW; Liu SJ; Lizarraga SB. ASJ1L regulates the structural development of neuronal circuitry by modulating BDNF/TrkB signalling in human neurons. bioRxiv https://doi.org/10.1101/2020.02.18.954586. : (2020).
• Shlevkov E; Basu H; Bray M-A; Sun Z' Wei W; Apaydin K; Karhohs K; Chen P-F; Smith JLM; Wiskow O; Roet K; Huang X; Effan K; Carpenter AE; Kleiman RJ; Schwarz TL. A High-Content Screen Identifies TPP1 and Aurora B as Regulators of Axonal Mitochondrial Transport. Cell Rep 28:749 (2019).
• Leibel SL; Winquist A; Tseu I; Wang J; Luo D; Shojaie S; Nathan N; Snyder E; Post M. Reversal of Surfactant Protein B Deficiency in Patient Specific Human Induced Pluripotent Stem Cell Derived Lung Organoids by Gene Therapy. Sci Rep 9:745 (2019).
• Durens M; Nestor J; Herold K Niescier RF; Lunden FW; Phillips AW; Lin Y-C; Nestor MW. High-content interrogation of human induced pluripotent stem cell-derived cortical organoid platforms. bioRxiv http://dx.doi.org/10.1101/697623. : (2019).
• Wu C; Watts ME; Rubin LL. MAP4K4 Activation Mediates Motor Neuron Degeneration in Amyotrophic Lateral Sclerosis. Cell Reports 26:1143-1156.e5 (2019).
• Adkar SS; Wu C-L; WIllard VP; Dicks A; Ettyreddy A; Steward N; Bhutani N; Gersbach CA; Guilak F. Step‐Wise Chondrogenesis of Human Induced Pluripotent Stem Cells and Purification Via a Reporter Allele Generated by CRISPR‐Cas9 Genome Editing. Stem Cells 37:65-76 (2019).
• Javed AO; Li Y; Muffat J; Su K-C; Cohen MA; Lungjangwa T; Auborg P; Cheeseman IM; Jaenisch R. Microcephaly Modeling of Kinetochore Mutation Reveals a Brain-Specific Phenotype. Cell Rep 25:368-382.e5 (2018).
• Zhang B; He L; Liu Y; Zhang J; Zeng Q; Wang S; Fan Z; Fang G; Chen L; Lv Y; Xi J; Yue W; Li Y; Pei X. Prostaglandin E2 is required for BMP4-induced mesoderm differentiation of human embryonic stem cells . Stem Cell Reports doi.org/10.1016/j.stemcr.2018.01.024: (2018).
• Peng Y; Xie M; Duan X; Hu L; Yu J; Zeng S; Wange Y; Ouang Q; Lu G; Lin G; Sun Y. Generation of a luciferase-expressing human embyronic stem cell line: NERCe002-A-2. Stem Cell Research doi.org/10.1016/j.scr.2018.02.010: (2018)
• Grow DA; Simmons DV; Gomez JA; Wanat MH; McCarrey JR; Paladini CA; Navara CS. Differentiation and characterizaton of dopaminergic neurons from baboon induced pluripotent stem cells. Stem Cells Transl Med 5:1133-44 (2016).
• Yang J; Kaur K; Ong LL; Eisenberg CA; Eisenberg LM. Inhibition of G9a histone methyltransferase converts bone marrow mesenchymal stem cells to cardiac competent progenitors. Stem Cells International Article 270428 (2015). doi:10.1155/2015/270428.
• DeRosa BA; Belle KC; Thomas BJ; Cukier HN; Pericak-Vance MA; Vance JM; Dykxhoom DM. hVGAT-mCherry: A novel molecular tool for analysis of GABAergic neurons derived from human pluripotent stem cells. Mol Cell Neurosci 68:244 (2015).