Dorsomorphin dihydrochloride

SKU: orb1301035

Description

Dorsomorphin dihydrochloride (BML-275 2HCl) is a selective, ATP-competitive AMPK inhibitor (Ki=109 nM) that also blocks BMP receptors ALK2, ALK3, and ALK6. This compound induces autophagy and exhibits antitumor activity, making it a valuable tool for studying metabolic signaling, bone morphogenesis, and cancer biology in both cellular and animal models.

Research Area

Cell Biology, Epigenetics & Chromatin, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 1219168-18-9
• MW: 472.41
• Purity: 98.75%
• Formula: C₂₄H₂₅N₅O·2HCl
• SMILES: Cl.Cl.C(CN1CCCCC1)Oc1ccc(cc1)-c1cnc2c(cnn2c1)-c1ccncc1
• Target: AMPK,Autophagy,TGF-beta/Smad
• Solubility: DMSO:7.4 mg/mL (15.66 mM);H2O:47.2 mg/mL (99.91 mM)

Bioactivity

• Target IC50:
  MCF-7 cells:4.9 μM (EC50)|A2780 cells:0.9 μM (EC50)|MP46 cells:10.13 µM|AMPK:109 nM (Ki)|OMM2. Cells:31.45 µM|92-1 cells:6.526 µM|HeLa cells:10.71 μM|Mel 270 cells:8.39 µM|HCT116 cells:11.34 μM
• In Vivo:
  6 h after dorsomorphin was administered intravenously, hepatic hepcidin mRNA levels were reduced to one-third of that of Vehicle-injected mice. Alterations in hepcidin levels affect serum iron concentration within 24 h vi the altered mobilization of intracellular iron by ferroportin33. Administration of dorsomorphin over 24 h led to a 60% increase in total serum iron concentration .
• In Vitro:
  Dorsomorphin (compound C) is a potent reversible inhibitor that is competitive with ATP, with Ki = 109 ± 16 nM in the absence of AMP. Incubation of cultured hepatocytes with compound C inhibited ACC inactivation by either AICAR or metformin. Compound C suppressed 2-deoxy-D-glucose (2DG)-induced GRP78 promoter activity in a dose-dependent manner but had little effect on tunicamycin-induced GRP78 promoter activity. Compound C also suppressed GRP78 promoter activity induced by glucose withdrawal.
• Cell Research:
  C2C12 cells were seeded into 96-well plates at 2,000 cells per well in DMEM supplemented with 2% FBS. Wells were treated in quadruplicate with BMP li and and dorsomorphin or Vehicle. Cells were Harvested after 5 d in culture with 50 μL Tris-buffered saline, 1% Triton X-100. Lysates were added to p-nitro-phenylphosphate reagent in 96-well plates for 1 h, and alkaline phosphatase activity expressed as absorbance at 405 nM. Cell viability and quantity were measured by Cell-titer Glo and binding of nuclear dye CyQuant, respectively using replicate wells treated identically to those used for alkaline phosphatase measurements.
• Animal Research:
  12-week-old C57B-/- mice raised on a standard diet were injected via the tail vein with 0.2 g/kg of dextran (average MW = 5,000) or 0.2 g/kg of iron-dextran USP. Dextran was injected with vehicle only, whereas iron-dextran was injected with either vehicle or dorsomorphin (10 mg/kg). 1 h after injection, mice were euthanized and liver segments were collected in 500 µL of SDS-lysis buffer and mechanically homogenized. 20 µL of liver extracts were resolved by SDS-PAGE and immunoblotted. Total RNA was harvested using Trizol from mechanically homogenized mouse livers (6 h after injection with a single intraperitoneal dose of dorsomorphin (10 mg/kg) or DMSO).

Storage & Handling

• Storage: store under nitrogen | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

inhibit, pathway, Inhibitor, Compound C Dihydrochloride, Compound C, Compound C 2HCl, Compound C dihydrochloride, Dorsomorphin, Dorsomorphin (Compound C), Dorsomorphin Dihydrochloride, Dorsomorphin dihydrochloride, Dorsomorphin (Compound C) 2HCl, AMPK, AMP-activated protein kinase, Autophagy, ATP-competitive, BML 275, BML 275 Dihydrochloride, BML275, BML-275, BML-275 2HCl, BML275 Dihydrochloride, BML-275 Dihydrochloride, BML-275 dihydrochloride, BMP, receptors, Smad, type, Transforming growth factor beta receptors, TGF-b/Smad, TGFb, TGFbeta/Smad, TGF-beta, TGFbeta, TGFβ, TGF-β Receptor, TGF-β/Smad

Compound Identifiers

PubChem CID

49761481