Dorsomorphin dihydrochloride [AMPK; ALK2; ALK3; ALK6 Inhibitor]
[CAT#: MOD2005ZP85]
A highly potent, selective AMPK inhibitor. Also promotes cardiomyocyte differentiation in mouse embroynic stem cells (mESCs).
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Description
Highly efficient, selective and reversible AMPK inhibitor (Ki = 109 nM). Inhibits AICAR and metformin-induced AMPK activation.It also exhibits activity in ALK2, ALK3 and ALK6. It also promote cardiomyocyte differentiation in mouse embryonic stem cells (mESCs).
Synonyms
Compound C; BML-275
Chemical Name
6-[4-[2-(1-Piperidinyl)ethoxy]pheny l]-3-(4-pyridinyl)-pyrazolo[1,5-a]pyrimidine dihydrochloride
Modulator Type
Inhibitor
Relevant Disease
Neurological Disorders
Assay Description
Dorsomorphin (Compound C) (0-10 μM, 18 h) inhibited 2DG-induced GRP78 promoter activity in human fibrosarcoma HT1080 cells in a dose-dependent manner, but had little effect on GRP78 promoter activity induced by tunicamycin. Dorsomorphin (Compound C) C also inhibits GRP78 promoter activity caused by glucose withdrawal. Dorsomorphin (Compound C) has no effect on 2DG-induced PERK activation in HT1080 cells, and reduces basal and 2DG-induced AMPK phosphorylation levels [1].
Assay Type
Western Blot Analysis
Cell Line
Human fibrosarcoma HT1080 cells.
Concentration
0-10 μM
Incubation Time
18 hours
Result
In a dose-dependent manner, 2DG-induced GRP78 promoter activity was inhibited, and glucose withdrawal-induced GRP78 promoter activity was also inhibited.
Reference
[1]. Saito S, et al. Compound C prevents the unfolded protein response during glucose deprivation through a mechanism independent of AMPK and BMP signaling. PLoS One. 2012;7(9):e45845.
Assay Description
Dorsomorphin (Compound C: 10 mg/kg, once intravenously) treatment can lead to a 60% increase in total serum iron levels in adult mice, reduce the basal level of hepcidin, and increase serum iron levels [1].
Dorsomorphin (Compound C: 0.2 mg/kg, intravenously 30 minutes before LPS injection) can reduce the expression of ICAM-1 and VCAM-1 in the aorta of LPS-injected rats [2].
Compared with animals stimulated with LPS only, treatment with Dorsomorphin (Compound C; 25 mg/kg; i.p. injection, in male BALB/c mice) before lipopolysaccharide (LPS) injection significantly reduced the lethality.
Dorsomorphin (Compound C: 0.2 mg/kg, intravenously 30 minutes before LPS injection) can reduce the expression of ICAM-1 and VCAM-1 in the aorta of LPS-injected rats [2].
Compared with animals stimulated with LPS only, treatment with Dorsomorphin (Compound C; 25 mg/kg; i.p. injection, in male BALB/c mice) before lipopolysaccharide (LPS) injection significantly reduced the lethality.
Animal Model
Wild-type (WT) C57BL/6 adult mice fed a standard iron supplemented diet express high levels of hepcidin
Dosage
10 mg/kg
Administration
Intravenously once.
Result
Increase serum total iron concentration by 60%. Effectively reduce the basal level of heparin expression in adult mice and increase serum iron concentration.
References
[1]. Yu PB, et al. Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol. 2008 Jan;4(1):33-41.
[2]. Kim YM, et al. Compound C independent of AMPK inhibits ICAM-1 and VCAM-1 expression in inflammatory stimulants-activated endothelial cells in vitro and in vivo. Atherosclerosis. 2011 Nov;219(1):57-64.
[2]. Kim YM, et al. Compound C independent of AMPK inhibits ICAM-1 and VCAM-1 expression in inflammatory stimulants-activated endothelial cells in vitro and in vivo. Atherosclerosis. 2011 Nov;219(1):57-64.
Molecular Weight
472.41
Form
Powder
Chemical Formula
C24H25N5O.2HCl
Source
Synthetic
SMILES
C1CCN(CC1)CCOC2=CC=C(C=C2)C3=CN4C(=C(C=N4)C5=CC=NC=C5)N=C3.Cl.Cl
Solubility
Soluble in water (100mM), and in DMSO (20mM)
CAS NO.
1219168-18-9
PubChem Substance ID
49761481
Purity
>98%
Storage
Room temperature (desiccate)
Shipping
Room Temperature
Handling Advice
For obtaining a higher solubility, please warm the tube at 37 °C and shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.
Research Use Only
For research use only
For Research Use Only. Not For Clinical Use.
