Molecular Weight (MW)

472.41

Formula

C24H25N5O.2HCl

CAS No.

1219168-18-9

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO:94 mg/mL (199 mM)

Water: <1 mg/mL

Ethanol: <1 mg/mL

Solubility (In vivo)

PBS: 15 mg/mL

Synonyms

Compound C; BML275; BML 275; BML-275; CpdC

Chemical Name: 6-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidine dihydrochloride

InChi Key: RJDVIJJQKMGPMV-UHFFFAOYSA-N

InChi Code: InChI=1S/C24H25N5O.2ClH/c1-2-12-28(13-3-1)14-15-30-22-6-4-19(5-7-22)21-16-26-24-23(17-27-29(24)18-21)20-8-10-25-11-9-20;;/h4-11,16-18H,1-3,12-15H2;2*1H

SMILES Code: [H]Cl.[H]Cl.C12=C(C3=CC=NC=C3)C=NN1C=C(C4=CC=C(OCCN5CCCCC5)C=C4)C=N2

In Vitro

In vitro activity: 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.Inhibition of AMPK activity by Dorsomorphin almost completely inhibits autophagic proteolysis in HT-29 cells. 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.

Kinase Assay: Dorsomorphin dihydrochloride (BML-275 dihydrochloride; Compound C dihydrochloride) is a potent, selective and ATP-competitive AMPK inhibitor, with a Ki of 109 nM. Dorsomorphin dihydrochloride inhibits BMP pathway by targeting the type I receptors ALK2, ALK3, and ALK6.

Cell Assay: Dorsomorphin (compound C) (0-10 μM, 18 h) suppresses 2DG-induced GRP78 promoter activity in human fibrosarcoma HT1080 cells in a dose-dependent manner but has little effect on tunicamycin-induced GRP78 promoter activity. Dorsomorphin (compound C) C also suppresses GRP78 promoter activity induced by glucose withdrawal. Dorsomorphin (compound C) has no effect on 2DG-induced PERK activation and reduces the both basal and 2DG-induced AMPK phosphorylation levels in HT1080 cells

In Vivo

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

Animal model

Iron-replete mice

Formulation & Dosage

Dissolved in DMSO; 10 mg/kg; i.v. administration

References

Nat Chem Biol. 2008 Jan;4(1):33-41; Atherosclerosis. 2011 Nov;219(1):57-64. (3):302-15.