Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Dorsomorphin dihydrochloride (BML-275 2HCl) is a potent, selective and ATP-competitive AMPK inhibitor (Ki: 109 nM) and does not exhibit significant activity on structurally related kinases.
Pack Size | Availability | Price/USD | Quantity |
---|---|---|---|
5 mg | In stock | $ 47.00 | |
10 mg | In stock | $ 64.00 | |
25 mg | In stock | $ 137.00 | |
50 mg | In stock | $ 247.00 | |
100 mg | In stock | $ 447.00 | |
500 mg | In stock | $ 987.00 | |
1 mL * 10 mM (in DMSO) | In stock | $ 52.00 |
Description | Dorsomorphin dihydrochloride (BML-275 2HCl) is a potent, selective and ATP-competitive AMPK inhibitor (Ki: 109 nM) and does not exhibit significant activity on structurally related kinases. |
Targets&IC50 | AMPK:109 nM (cell free) |
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 [1]. 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 [2]. |
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 concentrations within 24 h via the altered mobilization of intracellular iron by ferroportin33. Administration of dorsomorphin over 24 h led to a 60% increase in total serum iron concentrations [3]. |
Kinase Assay | Liver AMPK was partially purified from male SD rats to the blue-Sepharose step. The 100-μl reaction mixture contained 100 μM AMP, 100 μM ATP (0.5 μCi 33P-ATP per reaction), and 50 μM SAMS in a buffer (40 mM HEPES, pH 7.0, 80 mM NaCl, 0.8 mM EDTA, 5 mM MgCl2, 0.025% BSA, and 0.8 mM DTT). The reaction was initiated with the addition of the enzyme. After a 30-minute incubation at 30°C, the reaction was stopped by addition of 80 μl 1% H3PO4. Aliquots (100 μl) were transferred to 96-well MultiScreen plates. The plate was washed three times with 1% H3PO4 followed by detection in a Top-count. The in vitro AMPK inhibition data obtained with compound C — (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine — were fit to the following equation for competitive inhibition by nonlinear regression using a least-squares Marquardt algorithm in a computer program written by N. Thornberry of Merck Research Laboratories: Vi/Vo = (Km + S)/[S + Km × (1 + I/Ki)], where Vi is the inhibited velocity, Vo is the initial velocity, S is the substrate (ATP) concentration, Km is the Michaelis constant for ATP, I is the inhibitor (compound C) concentration, and Ki is the dissociation constant for compound C [1]. |
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 ligands 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 [3]. |
Animal Research | 12-week-old C57BL/6 mice raised on a standard diet were injected via the tail vein with 0.2 g kg?1 of dextran (average MW = 5,000) or 0.2 g kg?1 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 killed 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) [3]. |
Synonyms | BML-275 2HCl, Compound C dihydrochloride, Dorsomorphin (Compound C) 2HCl, Compound C 2HCl, BML-275 dihydrochloride |
Molecular Weight | 472.41 |
Formula | C24H25N5O·2HCl |
CAS No. | 1219168-18-9 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 10 mM, with gentle warming
H2O: 47.2 mg/mL (100 mM)
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Dorsomorphin dihydrochloride 1219168-18-9 Autophagy Chromatin/Epigenetic PI3K/Akt/mTOR signaling Stem Cells AMPK TGF-beta/Smad Dorsomorphin (Compound C) Compound C BML 275 BML275 Dihydrochloride Dorsomorphin BMP TGF-β Receptor Compound C Dihydrochloride Dorsomorphin Dihydrochloride inhibit BML-275 2HCl BML-275 Dihydrochloride Compound C dihydrochloride type ATP-competitive BML 275 Dihydrochloride Dorsomorphin (Compound C) 2HCl Transforming growth factor beta receptors receptors Compound C 2HCl BML-275 dihydrochloride pathway BML-275 AMP-activated protein kinase Inhibitor BML275 inhibitor