Dorsomorphin (Compound C) dihydrochloride

Biological Activity

Dorsomorphin dihydrochloride is a potent inhibitor of AMP-activated protein kinase (AMPK) (Ki = 109 nM) and bone morphogenic protein (BMP) signaling. Dorsomorphin dihydrochloride inhibits AMPK activation induced by AICAR and metformin. Dorsomorphin dihydrochloride also inhibits the bone morphogenetic protein type 1 receptors ACTR-I (ALK2), BMPR-IA (ALK3), and BMPR-IB (ALK6). Dorsomorphin dihydrochloride induces autophagy in cancer cell lines via a mechanism independent of AMPK inhibition.

Product Citations

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  Indian J Pharm Sci. 2022;2022:84(3)284-293.

  Gallic acid Inhibits M1 Macrophage Polarization via Adenosine 5'-Monophosphate-Activated Protein Kinase/Signal Transducers and Activators of
  Dorsomorphin (Compound C) dihydrochloride purchased from AbMole

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  Acta Histochem. 2022 Aug;124(6):151931.

  Fibroblast-derived exosomal miRNA-133 promotes cardiomyocyte-like differentiation
  Dorsomorphin (Compound C) dihydrochloride purchased from AbMole

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  J Food Biochem. 2022 Aug 5;e14351.

  Liquiritin inhibits H2O2-induced oxidative stress injury in H9c2 cells via the AMPK/SIRT1/NF-κB signaling pathway
  Dorsomorphin (Compound C) dihydrochloride purchased from AbMole

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  Int J Mol Sci. 2023 Jan 5;24(2):1070.

  Sulforaphane Suppresses H2O2-Induced Oxidative Stress and Apoptosis via the Activation of AMPK/NFE2L2 Signaling Pathway in Goat Mammary Epithelial Cells
  Dorsomorphin (Compound C) dihydrochloride purchased from AbMole

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  Adv Sci (Weinh) . 2022 Nov 22;10(1):e2204463.

  Genetic and Pharmacological Inhibition of Astrocytic Mysm1 Alleviates Depressive-Like Disorders by Promoting ATP Production
  Dorsomorphin (Compound C) dihydrochloride purchased from AbMole

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  Int J Biol Sci. 2022 Jan 31;18(4):1594-1611.

  Atractylenolide III ameliorates Non-Alcoholic Fatty Liver Disease by activating Hepatic Adiponectin Receptor 1-Mediated AMPK Pathway
  Dorsomorphin (Compound C) dihydrochloride purchased from AbMole

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  Front Pharmacol. 2021 May 17;12:589273.

  Dapagliflozin Alleviates Hepatic Steatosis by Restoring Autophagy via the AMPK-mTOR Pathway
  Dorsomorphin (Compound C) dihydrochloride purchased from AbMole

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  Front Oncol. 2021 Jan 29;10:614067.

  Solasonine Suppresses the Proliferation of Acute Monocytic Leukemia Through the Activation of the AMPK/FOXO3A Axis
  Dorsomorphin (Compound C) dihydrochloride purchased from AbMole

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  BMC Cancer. 2021 Feb 25;21(1):195.

  Blockage of AMPK-ULK1 pathway mediated autophagy promotes cell apoptosis to increase doxorubicin sensitivity in breast cancer (BC) cells: an in vitro study
  Dorsomorphin (Compound C) dihydrochloride purchased from AbMole

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  J Cell Physiol. 2021 Mar;236(3):1889-1902.

  Icariin ameliorates endothelial dysfunction in type 1 diabetic rats by suppressing ER stress via the PPARα/Sirt1/AMPKα pathway
  Dorsomorphin (Compound C) dihydrochloride purchased from AbMole

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  Cell Physiol Biochem. 2018;50(6):2341-2364.

  Peperomin E Induces Promoter Hypomethylation of Metastatic-Suppressor Genes and Attenuates Metastasis in Poorly Differentiated Gastric Cancer.
  Dorsomorphin (Compound C) dihydrochloride purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Hum Mol Genet (2016). Figure 2. Dorsomorphin dihydrochloride
	Method	RT-qPCR
	Cell Lines	iPSC lines
	Concentrations	1 μM
	Incubation Time	72 h
	Results	We generated cortical neurons using a well-established protocol with small molecule dual SMAD inhibition for neural induction followed by plating of neuroepithelial cells for final differentiation

Protocol (for reference only)

Cell Experiment
Cell lines	Spermatogonial Cell
Preparation method	Dorsomorphin was added to the medium at a final concentration of 0, 1, 2, 4, or 8 µM (in final 0.4% dimethyl sulfoxide). The cells were maintained at 28.5°C in an atmosphere of 3% carbon dioxide and the medium was replaced every 3–4 days.
Concentrations	0, 1, 2, 4, or 8 µM
Incubation time	3 weeks

Animal Experiment
Animal models	C57BL/6 mice
Formulation	DMSO
Dosages	10 mg/kg
Administration	i.p.

Chemical Information

Molecular Weight	472.41
Formula	C24H25N5O.2HCl
CAS Number	1219168-18-9
Solubility (25°C)	Water 45 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Wong TT, et al. PLoS One. Dorsomorphin promotes survival and germline competence of zebrafish spermatogonial stem cells in culture.

[2] Hyeon Ung Park, et al. Mol Cancer Ther. AMP-activated protein kinase promotes human prostate cancer cell growth and survival

[3] Yu PB, et al. Nat Chem Biol. Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism.