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.

Stemgent and the Stemolecule brand name are trademarks of REPROCELL Inc., Japan.

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.

Specification Sheets:

• 04-0024 Specifications Sheet

Safety Data Sheets:

• 04-0024 Safety Data Sheet

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

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• Werder RB; Liu T; Abo KM; Lindstrom-Vautrin J; Villacorta-Martin C; Huang J; Hinds A; Boyer N; Bullitt E; Liesa M; Silverman EK; Kotton DN; Cho MH; Zhou X; Wilson AA. CRISPR interference interrogation of COPD GWAS genes reveals the functional significance of desmoplakin in iPSC-derived alveolar epithelial cells. Sci Adv 8:eabo6566 (2022).
• Colombo L. “Trans-neuromuscular spreading of mutant Huntingtin: a novel pathway for Huntington’s disease skeletal muscle pathology. Ph. D. Thesis, Universität Basel : (2022).
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• Geusz RJ; Wang A; Lam DK; Vinckier NK; Alysandratos K-D; Roberts DA; Wang J; Kefalopoulou S; Ramirez A; Qiu Y; Chiou J; Gaulton KJ; Ren B; Kotton DN; Sander M. Sequence logic at enhancers governs a dual mechanism of endodermal organ fate induction by FOXA pioneer factors. Nature Commun 12:6636 (2022).
• Li H; Jiang H; Li L; Yan Z; Feng J. Generation of human A9 dopaminergic pacemakers from induced pluripotent stem cells. Molec Phychiatry 44682:DOI: 10.1038/s41380-022-01628-1 (2022).
• Yeo G; xiang J; Mueller J; Luo E-C; Yee B; Schafer D; Schmok J; Tan F; Rothamel K; McVicar R; Kwong E; Croker B; Jones K; Her H-L; Chen C-Y; Vu A; Jin W; Park S; Le P; Brennan K; Kofman E; Li Y; Tankka A; Dong K; Song Y; Clark A; Carlin A; Van Nostrand E; Leibel S. Discovery and functional interrogation of SARS-CoV2 protein-RNA interactions. Research Square :doi.org/10.21203/rs.3.rs-1394331/v1 (2022).
• Lu V. The Role of Glutamine in Primed Human Pluripotent Stem Cell Fate. Ph.D. Theses, University of California, Los Angeles : (2022).
• 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).