Dorsomorphin (Compound C)

Catalog No.S7840 Synonyms: BML-275,Compound C

Dorsomorphin (Compound C) Chemical Structure

Molecular Weight(MW): 399.49

Dorsomorphin is a potent, reversible, selective AMPK inhibitor with Ki of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Also inhibits type I BMP receptor activity.

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6 Customer Reviews

  • (A) Cells were pre-treated with 10 ng/ml TGF-β for 24 h, then 5 mM metformin and/or 1 uM (μM) dorsomorphin were added to the medium for another 24 h. Immunofluorescence staining showed that AMPK inhibition abolished metformin's effect of decreasing TGF-β-induced α-actin expression in HFL-1 cells. The nucleus were stained with 4', 6-diamidino-2-phenylindole in the merged images. Scale bars: 150 μm.

    Oncotarget, 2016, 6(41):43605-19.. Dorsomorphin (Compound C) purchased from Selleck.

    FGF21 activates myogenic and aerobic myofiber-associated genes expression via AMPK pathway. The activator (acadesine) or inhibitor (dorsomorphin) of AMPK pathway were used to treat the pcDNA3.1-21 or control transfected C2C12 myoblasts. For this experiment, four groups were set up: FGF21-ACA (pcDNA3.1-21‡acadesine), Control-ACA (control‡acadesine), FGF21-DOR (pcDNA3.1-21‡dorsomorphin), and Control-DOR(control‡dorsomorphin). The qRT-PCR was performed to detect the genes expression of FGF21 (A), AMPK (B), Sirt 1, Myoglobin(C), Desmin (D), MEF2c (E), a-actin (F). (G) The C2C12 myoblasts were transiently transfected with pCDNA3.1-21 or pCDNA3.1, Western blot showed FGF21 activated AMPK signal via FGF21-Sirt1-AMPK. For the phosphorylated AMPK (right), the intensity of band was normalized total AMPK, and then normalized by control. (H and I) FGF21, as well as AMPK activator acadesine (ACA), increased phosphorylation of AMPM, and myogenic genes expression, especially MyHC I, which was activated by ACA (FGF21‡ACA) and suppressed by AMPK inhibitor DOR(FGF21‡DOR). The data are presented as mean±SD (*P<0.05, **P<0.01, and P<0.001), n=ˆ3.

    J Cell Physiol, 2016.. Dorsomorphin (Compound C) purchased from Selleck.

  • ZLN005 increased autophagic activities in cardiomyocytes under HG conditions by SIRT1 pathway. LC3, ATG5, Beclin1, and SIRT1 expression of cardiomyocytes was measured by Western blot analysis. EX527: SIRT1-specific inhibitor. Compound C: AMPK-specific inhibitor Dorsomorphin. The results are expressed as the means±SEM, n=3. The value of LC3 II/LC3 I in ZLN005(−)EX527(−) groups was set as 1. (D): *P<0.05 compared with the ZLN005(−) Compound C(−) groups. ZLN005 (+): 4 μM. Compound C (+): 5 μM.

    Exp Cell Res, 2016, 345(1):25-36.. Dorsomorphin (Compound C) purchased from Selleck.

    Effect of dorsomorphin on MCP-1 and adiponectin production in TNFα-stimulated 3T3-L1 adipocytes with or without AICAR. 3T3-L1 cells were preincubated with 1–10 µM of dorsomorphin (Compound C) with or without 2 mM of AICAR for 1 h and then treated with 50 ng/ml of TNFα (TD1, TD3, TD10, and TAD1, TAD3, TAD10). After 24 h, the MCP-1 (a) and adiponectin (b) concentration in the culture medium was assayed. Data are means ± SD of five observations. D10: Only dorsomorphin treated cells. a: Control (C) vs T, TD1, TD3 or TD10: p < 0.001, T, TD1, TD3 or TD10 vs TA, TAD1, TAD3, TAD10 or D10: p < 0.001, TA vs C or D10: p < 0.05.b: C or D10 vs T, TD1, TD3 or TD10: p < 0.001, T vs TA or TAD3: p < 0.005, T vs TAD1: p < 0.01, T vs TAD10: p < 0.001, TD1, TD3 or TD10 vs TA, TAD3 or TAD10: p < 0.001, TD1, TD3 or TD10 vs TAD1: p < 0.005.

    J Atheroscler Thromb, 2016, 23(12):1345-1354.. Dorsomorphin (Compound C) purchased from Selleck.

  • Clin Exp Pharmacol Physiol, 2016, 43(1):125-34. . Dorsomorphin (Compound C) purchased from Selleck.

    Levels of phosphorylated AMPK, phosphorylated AKT, GK, PEPCK, and G6pase, PI3K in four groups were analyzed by Western blots in the presence of ASCs co-culturing for 12 h. C.C=compound C:Dorsomorphin, PA:palmitate, ASC:mesenchymal stem cells.

    Biochem Biophys Res Commun, 2017, 483(1):435-441.. Dorsomorphin (Compound C) purchased from Selleck.

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Notes:

2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.

Biological Activity

Description Dorsomorphin is a potent, reversible, selective AMPK inhibitor with Ki of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Also inhibits type I BMP receptor activity.
Targets
AMPK [1]
109 nM(Ki)
In vitro

Dorsomorphin inhibits ACC inactivation by either AICAR or metformin, and also attenuates AICAR and metformin’s effect to increase fatty acid oxidation or suppress lipogenic genes in hepatocytes. [1] Inhibition of AMPK activity by Dorsomorphin almost completely inhibits autophagic proteolysis in HT-29 cells. [2] in addition, Dorsomorphin selectively inhibits the BMP type I receptors ALK2, ALK3 and ALK6, and thus blocks BMP-mediated SMAD1/5/8 phosphorylation, target gene transcription and osteogenic differentiation. [3]

In vivo Dorsomorphin (10 mg/kg) reduces basal levels of hepcidin expression and increases serum iron concentrations in adult mice. [3] Dorsomorphin (0.2 mg/kg, i.v.) significantly reduces VCAM-1 and ICAM-1 expression in the thoracic aorta of LPS-treated rats. [4]

Protocol

Animal Research:[3]
+ Expand
  • Animal Models: Iron-replete mice
  • Formulation: DMSO
  • Dosages: ~10 mg/kg
  • Administration: i.v.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 3 mg/mL (7.5 mM) warming
Ethanol 2 mg/mL warmed (5.0 mM)
Water <1 mg/mL
In vivo

* 1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 399.49
Formula

C24H25N5O

CAS No. 866405-64-3
Storage powder
in solvent
Synonyms BML-275,Compound C

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID