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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Cited by 67 Publications

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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]
(Cell-free assay)
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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
mouse C2C12 cells M1\XNWZ2dmO2aX;uJIF{e2G7 MWq0JO69VQ>? NFjvSmtKdmirYnn0bY9vKG:oIFLNVHIyNW2nZHnheIVlKG:|dHXvZoxie3RiZHnm[oVz\W62aXH0bY9vKGmwIFLNVFQue3SrbYXsZZRm\CCvb4Xz[UBEOkNzMjDj[YxteyCjc4Pld5Nm\CCjczDk[YNz\WG|ZTDpckBidGujbHnu[UBxcG:|cHjheIF{\SCuZY\lcEBifCB2IIXNJIJ6KHOyZXP0do9xcG:2b33leJJ6 MnLLNVgxOjZyOUS=

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Assay
Methods Test Index PMID
Western blot
Id1 / Id2 / Id3 ; 

PubMed: 25010525     


Dorsomorphin dramatically inhibited the expression of Ids. KMM cells were treated with 5 µM Dorsomorphin for 24 hours before harvesting. Expressions of Ids were detected by immunoblotting. 

pAMPK / AMPK / pACC / ACC / pRaptor / HIF1α; 

PubMed: 29531259     


PC-3 and LNCaP cells were treated with vehicle, 25 µM compound 8c, 25 µM compound 8c + 5 μM Dorsomorphin (8c + D) or 5 μM Dorsomorphin (D), for 1 hour or 24 hours and levels of the phosphorylated AMPK (pAMPK), phosphorylated ACC (pACC), phosphorylated Raptor (pRaptor) forms and HIF1α were determined by Western blot. Upper panel, representative Western blot of three different experiments. β-tubulin (β-Tub) serves as a loading control. Lower panel, densitometric analyses of bands represented as the mean of the ratio pAMPK/AMPK or pACC/ACC. 

25010525 29531259
Immunofluorescence
p-AMPK / Sirt1 / p66Shc ; 

PubMed: 28728079     


Cellular immunofluorescence with anti-p-AMPK, anti-Sirt1 and anti-p66Shc antibodies. High levels of p-AMPK were observed under LG conditions and were accompanied by Sirt1 expression. HG reduced this fluorescence. This effect was reversed by probucol treatment and Dorsomorphin and EX-527 treatment but was increased by AICAR treatment. Contrasting results were observed regarding p66Shc and DHE staining (lower panel). 

28728079
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 Ethanol 2 mg/mL warmed (5.0 mM)
DMSO 1 mg/mL warmed (2.5 mM)
Water 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