| Size | Price | Stock | Qty |
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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Dorsomorphin 2HCl (formerly BML-275 dihydrochloride) is a reversible and selective AMPK (AMP-activated protein kinase) inhibitor that inhibits AMPK with a Ki of 109 nM in cell-free assays, exhibiting little inhibition against closely related kinases such as ZAPK, SYK, PKCθ, PKA, and JAK3. Additionally, dorsomorphin blocks the BMP signaling that encourages cardiomyogenesis in embryonic stem cells. Dorsomorphin inhibits bone morphogenetic protein signaling to change the mesenchymal phenotype of breast cancer initiating cells.
| Targets |
AMPK (Ki = 109 nM); ACVR1; BMPR1A; ALK6; Autophagy
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|---|---|
| ln 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]
In HT-29 cells, Dorsomorphin almost entirely prevents autophagic proteolysis by inhibiting AMPK activity.[2]
Additionally, Dorsomorphin blocks the BMP-mediated phosphorylation of SMAD1/5/8, target gene transcription, and osteogenic differentiation by specifically inhibiting the BMP type I receptors ALK2, ALK3, and ALK6.[3]
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| ln 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]
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| Enzyme Assay |
Liver AMPK is partially purified from male SD rats to the blue-Sepharose step. In a buffer of 40 mM HEPES, pH 7.0, 80 mM NaCl, 0.8 mM EDTA, 5 mM MgCl2, 0.025% BSA, and 0.8 mM DTT, 100 μl AMP, 100 μl ATP (0.5 μCi 33P-ATP per reaction), and 50 μM SAMS are present in the 100-l reaction mixture. As soon as the enzyme is added, the reaction starts. After 30-minute incubation at 30°C, the reaction is stopped by addition of 80 μl 1% H3PO4. Aliquots (100 μl) are transferred to 96-well MultiScreen plates. The plate is 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 — are 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.
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| Cell Assay |
Cells were treated with hydrogen peroxide and incubated in complete medium with or without treatment with the AMPK activators metformin (10 μM), AICAR (10 μM), alone or plus AMPK inhibitor Compound C (CC, 10 μM) for 3 days.
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| Animal Protocol |
Iron-replete mice
~10 mg/kg i.v. |
| References |
| Molecular Formula |
C24H27CL2N5O
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|---|---|
| Molecular Weight |
472.41008
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| Elemental Analysis |
C, 61.02; H, 5.76; Cl, 15.01; N, 14.82; O, 3.39
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| CAS # |
1219168-18-9
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| Related CAS # |
Dorsomorphin;866405-64-3;Dorsomorphin dihydrochloride;1219168-18-9
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| Appearance |
Solid powder
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| SMILES |
C1CCN(CC1)CCOC2=CC=C(C=C2)C3=CN4C(=C(C=N4)C5=CC=NC=C5)N=C3.Cl.Cl
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| InChi Key |
RJDVIJJQKMGPMV-UHFFFAOYSA-N
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| 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
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| Chemical Name |
6-[4-(2-piperidin-1-ylethoxy)phenyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidine;dihydrochloride
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| Synonyms |
Compound C; CpdC; BML275; BML-275; BML 275
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~94 mg/mL (~199 mM)
Water: <1 mg/mL Ethanol: <1 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 20 mg/mL (42.34 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).
Solubility in Formulation 2: PBS: 15mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1168 mL | 10.5840 mL | 21.1681 mL | |
| 5 mM | 0.4234 mL | 2.1168 mL | 4.2336 mL | |
| 10 mM | 0.2117 mL | 1.0584 mL | 2.1168 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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