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Potent inhibitor of AMP-activated protein kinase (AMPK) (Ki = 109 nM). Displays no significant activity on several structurally related kinases including ZAPK, SYK, PKCθ, PKA and JAK3. Inhibits AMPK activation induced by AICAR (Cat. No. 2840) and metformin (Cat. No. 2864). Also inhibits bone morphogenetic protein (BMP) type I receptors (ALK2, ALK3 and ALK6). Promotes cardiomyogenesis in mouse embryonic stem cells (ESCs) in vitro. Shown to induce autophagy in cancer cell lines via a mechanism independent of AMPK inhibition.
|Storage||Desiccate at RT|
The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.
|Solvent||Max Conc. mg/mL||Max Conc. mM|
|DMSO||9.45||20 with gentle warming|
Preparing Stock Solutions
The following data is based on the product molecular weight 472.41. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||2.12 mL||10.58 mL||21.17 mL|
|5 mM||0.42 mL||2.12 mL||4.23 mL|
|10 mM||0.21 mL||1.06 mL||2.12 mL|
|50 mM||0.04 mL||0.21 mL||0.42 mL|
References are publications that support the biological activity of the product.
Zhou et al (2001) Role of AMP-activated protein kinase in mechanism of MetF. action. J.Clin.Invest. 108 1167 PMID: 11602624
Yu et al (2008) Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat.Chem.Biol. 4 33 PMID: 18026094
Vucicevic et al (2011) Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt/mTOR pathway. Autophagy 7 40 PMID: 20980833
Hao et al (2008) Dorsomorphin, a selective small molecule inhibitor of BMP signaling, promotes cardiomyogenesis in embryonic stem cells. PLoS ONE 3 2904 PMID: 18682835
Diekmann et al (2015) A reliable and efficient protocol for human pluripotent stem cell differentiation into the definitive endoderm based on dispersed single cells. Stem Cells Dev. 24 190 PMID: 25137387
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56 Citations for Dorsomorphin dihydrochloride
Citations are publications that use Tocris products. Selected citations for Dorsomorphin dihydrochloride include:
Paonessa et al (2019) Microtubules Deform the Nuclear Membrane and Disrupt Nucleocytoplasmic Transport in Tau-Mediated Frontotemporal Dementia. Cell Rep 26 582 PMID: 30650353
Sellayah et al (2011) Orexin is required for brown adipose tissue development, differentiation, and function. Autophagy 14 478 PMID: 21982708
Al-Bayati et al (2016) Effects of thrombin on Ins signalling and glucose uptake in cultured human myotubes. J Diabetes Complications 30 1209 PMID: 27396242
Kapeli et al (2016) Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses Nature Communications 7 12143 PMID: 27378374
Mou et al (2016) Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells Cell: Stem Cell 19 217 PMID: 27320041
Vessoni et al (2016) Cockayne syndrome-derived neurons display reduced synapse density and altered neural network synchrony. Hum Mol Genet 25 1271 PMID: 26755826
Obba et al (2015) The PRKAA1/AMPKα1 pathway triggers autophagy during CSF1-induced human monocyte differentiation and is a potential target in CMML. Nat Protoc 11 1114 PMID: 26029847
Huang et al (2015) The in vitro generation of lung and airway progenitor cells from human pluripotent stem cells. Nat Genet 10 413 PMID: 25654758
Liao et al (2015) Targeted disruption of DNMT1, DNMT3A and DNMT3B in human embryonic stem cells. Exp Ther Med 47 469 PMID: 25822089
Zhu et al (2015) Adenosine monophosphate-activated protein kinase activation mediates the leptin-induced attenuation of cognitive impairment in a streptozotocin-induced rat model. Nature 9 1998 PMID: 26136928
Tsankov et al (2015) Transcription factor binding dynamics during human ES cell differentiation. Biomed Res Int 518 344 PMID: 25693565
Matsuda et al (2015) Comparative Study on the Cytoprotective Effects of Activated Protein C Treatment in Nonsteatotic and Steatotic Livers under Ischemia-Reperfusion Injury. BMC Neurosci 2015 635041 PMID: 26539519
Khan et al (2015) Blocking a vicious cycle nNOS/peroxynitrite/AMPK by S-nitrosoglutathione: implication for stroke therapy. J Pharmacol Exp Ther 16 42 PMID: 26174015
Sposito et al (2015) Developmental regulation of tau splicing is disrupted in stem cell-derived neurons from frontotemporal dementia patients with the 10 + 16 splice-site mutation in MAPT. Sci Rep 24 5260 PMID: 26136155
Palm et al (2015) Rapid and robust generation of long-term self-renewing human neural stem cells with the ability to generate mature astroglia. Int J Mol Sci 5 16321 PMID: 26541394
Chen et al (2015) Chemical constituents analysis and antidiabetic activity validation of four fern species from Taiwan. Exp Neurol 16 2497 PMID: 25622260
Holtzhausen et al (2014) Novel bone morphogenetic protein signaling through Smad2 and Smad3 to regulate cancer progression and development. FASEB J 28 1248 PMID: 24308972
Huang et al (2014) Efficient generation of lung and airway epithelial cells from human pluripotent stem cells. Nat Biotechnol 32 84 PMID: 24291815
Mourabit et al (2014) Bmp suppression in mangrove killifish embryos causes a split in the body axis. PLoS One 9 e84786 PMID: 24497921
Hsu et al (2018) Rab5 and Alsin regulate stress-activated cytoprotective signaling on mitochondria. Elife 7 PMID: 29469808
Kutsche et al (2018) Combined Experimental and System-Level Analyses Reveal the Complex Regulatory Network of miR-124 during Human Neurogenesis. Cell Syst 7 438 PMID: 30292704
Sheng et al (2018) A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation. Nat Commun 9 4047 PMID: 30279449
Kottakis et al (2016) LKB1 loss links serine metabolism to DNA methylation and tumorigenesis. Nature 539 390 PMID: 27799657
Park et al (2016) Ethanol extract of Kalopanax septemlobus leaf induces caspase-dependent apoptosis associated with activation of AMPK in human hepatocellular carcinoma cells. Int J Oncol 48 261 PMID: 26549816
Ahmed (2016) Effects of novel muscarinic M3 receptor ligand C1213 in pulmonary arterial hypertension models. Physiological Reports 4 e13069 PMID: 28039410
Virtanen et al (2014) Adenosine inhibits tumor cell invasion via receptor-independent mechanisms. Mol Cancer Res 12 1863 PMID: 25080434
Makanae et al (2014) Co-operative Bmp- and Fgf-signaling inputs convert skin wound healing to limb formation in urodele amphibians. Dev Biol 396 57 PMID: 25286122
Petersen et al (2012) Engineering artificial signaling centers to polarize embryoid body differentiation. Br J Pharmacol 21 647 PMID: 21958075
Shi et al (2012) Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses. FASEB J 15 477 PMID: 22306606
Caires-Júnior (2018) Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells. Nat Commun 9 475 PMID: 29396410
Nott et al (2016) Histone deacetylase 3 associates with MeCP2 to regulate FOXO and social behavior. Nat Neurosci 19 1497 PMID: 27428650
Puente et al (2016) Nutrient-regulated Phosphorylation of ATG13 Inhibits Starvation-induced Autophagy. J Biol Chem 291 6026 PMID: 26801615
Hou et al (2012) LirGlu., a long-acting GLP-1 mimetic, and its metabolite attenuate inflammation after intracerebral hemorrhage. J Cereb Blood Flow Metab 32 2201 PMID: 22968320
Duong et al (2012) BML-275, an AMPK inhibitor, induces DNA damage, G2/M arrest and apoptosis in human pancreatic cancer cells. Int J Oncol 41 2227 PMID: 23076030
Dai et al (2017) Methyl-β-cyclodextrin restores impaired autophagy flux in Niemann-Pick C1-deficient cells through activation of AMPK. Autophagy 13 1435 PMID: 28613987
Rempel et al (2015) A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol 89 1599 PMID: 26272509
Ueki et al (2015) A transient wave of BMP signaling in the retina is necessary for Müller glial differentiation. Development 142 533 PMID: 25605781
Fong et al (2013) Moderate excess of pyruvate augments osteoclastogenesis. Biol Open 2 387 PMID: 23616923
Reinhardt et al (2013) Derivation and expansion using only small molecules of human neural progenitors for neurodegenerative disease modeling. PLoS One 8 e59252 PMID: 23533608
Ueki and Reh (2013) EGF stimulates Müller glial proliferation via a BMP-dependent mechanism. Glia 61 778 PMID: 23362023
Sheehan-Rooney et al (2013) Bmp and Shh signaling mediate the expression of satb2 in the pharyngeal arches. PLoS One 8 e59533 PMID: 23555697
Knelson et al (2013) Type III TGF-β receptor promotes FGF2-mediated neuronal differentiation in neuroblastoma. J Clin Invest 123 4786 PMID: 24216509
Kim et al (2013) Epigallocatechin gallate (EGCG) stimulates autophagy in vascular endothelial cells: a potential role for reducing lipid accumulation. J Biol Chem 288 22693 PMID: 23754277
Dhillon and Belsham (2011) Estrogen inhibits NPY secretion through membrane-associated estrogen receptor (ER)-α in clonal, immortalized hypothalamic neurons. Int J Obes (Lond) 35 198 PMID: 20548307
Lou et al (2011) Smarcd3b and Gata5 promote a cardiac progenitor fate in the zebrafish embryo. Development 138 3113 PMID: 21715426
Bumpus and Johnson (2011) 5-Aminoimidazole-4-carboxyamide-ribonucleoside (AICAR)-stimulated hepatic expression of Cyp4a10, Cyp4a14, Cyp4a31, and other peroxisome proliferator-activated receptor α-responsive mouse genes is AICAR 5'-monophosphate-dependent and AMP-activated Hum Mol Genet 339 886 PMID: 21896918
Takata et al (2017) Self-patterning of rostral-caudal neuroectoderm requires dual role of Fgf signaling for localized Wnt antagonism. Nat Commun 8 1339 PMID: 29109536
Morizane and Bonventre (2017) Generation of nephron progenitor cells and kidney organoids from human pluripotent stem cells. Nat Protoc 12 195 PMID: 28005067
Song et al (2017) Single-Cell Alternative Splicing Analysis with Expedition Reveals Splicing Dynamics during Neuron Differentiation. Mol Cell 67 148 PMID: 28673540
Nguyen et al (2017) DGAT1-Dependent Lipid Droplet Biogenesis Protects Mitochondrial Function during Starvation-Induced Autophagy. Dev Cell 42 9 PMID: 28697336
Lin et al (2017) Lactate-activated macrophages induced aerobic glycolysis and epithelial-mesenchymal transition in breast cancer by regulation of CCL5-CCR5 axis: a positive metabolic feedback loop. Oncotarget 8 110426 PMID: 29299159
Graham et al (2014) BMP signalling regulates the pre-implantation development of extra-embryonic cell lineages in the mouse embryo. Nat Neurosci 5 5667 PMID: 25514175
Taub et al (2013) Distinct energy requirements for human memory CD4 T-cell homeostatic functions. Stem Cells Dev 27 342 PMID: 22972918
Pol et al (2013) Sox10-MCS5 enhancer dynamically tracks human oligodendrocyte progenitor fate. Lab Chip 247 694 PMID: 23507034
Li et al (2013) Flow-based pipeline for systematic modulation and analysis of 3D tumor microenvironments. Nat Commun 13 1969 PMID: 23563587
Brafman et al (2013) Regulation of endodermal differentiation of human embryonic stem cells through integrin-ECM interactions. Cell Metab 20 369 PMID: 23154389
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On acute brain slices, to investigate the role of AMP kinase. The effect was minimal but close to what was expected.
30 minute pre-incubation
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