1. Epigenetics
    PI3K/Akt/mTOR
    Autophagy
  2. AMPK
    Autophagy

Dorsomorphin dihydrochloride (Synonyms: BML-275 dihydrochloride; Compound C dihydrochloride; BML275 dihydrochloride; BML 275 dihydrochloride)

Cat. No.: HY-13418 Purity: 99.73%
Data Sheet SDS Handling Instructions

Dorsomorphin dihydrochloride is a potent and selective AMPK inhibitor, that is competitive with ATP, with Ki of 109±16 nM in the absence of AMP.

For research use only. We do not sell to patients.
Dorsomorphin dihydrochloride Chemical Structure

Dorsomorphin dihydrochloride Chemical Structure

CAS No. : 1219168-18-9

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Other Forms of Dorsomorphin dihydrochloride:

Top Publications Citing Use of Products

    Dorsomorphin dihydrochloride purchased from MCE. Usage Cited in: Biochem Pharmacol. 2017 May 19. pii: S0006-2952(17)30260-5.

    Dose-dependent effects of Cantharidin on AMPK-related signaling in three HCC cell lines. The phosphorylation of AMPK is markedly upregulated, and so is its downstream effector phospho-ULK1, whereas PP5 expression is not affected after Cantharidin treatment.

    Dorsomorphin dihydrochloride purchased from MCE. Usage Cited in: Biochem Pharmacol. 2017 May 19. pii: S0006-2952(17)30260-5.

    Blockade of AMPK signals by AMPK α2 siRNA or AMPK inhibitor (Dorsomorphin; 2.5 μM, pretreatment 2 hours) treatment counteracts the apoptotic effects of Cantharidin at 2.5 μM. Data are representative of at least two independent experiments. Blocking AMPK signaling by knockdown of AMPK or Dorsomorphin (AMPK kinase inhibitor) treatment markedly reverses the apoptotic effect of Cantharidin, indicating that AMPK activation is required for the anti-HCC activity of Cantharidin.

    Dorsomorphin dihydrochloride purchased from MCE. Usage Cited in: Biochem Pharmacol. 2017 May 19. pii: S0006-2952(17)30260-5.

    PP5 overexpression suppresses AMPK-Thr172 phosphorylation induced by AMPK activators, AICAR and metformin. Hep3B cells are transfected with indicated plasmids and treated with AICAR (2 mM; 3 h) or Metformin (3 mM; 16 h) to simulate AMPK phosphorylation.

    Dorsomorphin dihydrochloride purchased from MCE. Usage Cited in: Mol Oncol. 2017 Apr 28.

    Effects of Palbociclib on CDK4/6-Rb pathway. HCC cells are treated with different doses of Palbociclib for 24 h, and then, the cells are subjected to western blot analysis.

    Dorsomorphin dihydrochloride purchased from MCE. Usage Cited in: Mol Oncol. 2017 Apr 28.

    Inhibition of AMPK reverses Palbociclib-induced autophagy and apoptosis. Hep3B cells are incubated with AMPK inhibitor (Compound C, 2.5 μM) for 4 h and then treated with Palbociclib for 24 h. Apoptotic cells are determined by flow cytometry.

    Dorsomorphin dihydrochloride purchased from MCE. Usage Cited in: Mol Oncol. 2017 Apr 28.

    Effects of CDK4/6 inhibitors on AMPK phosphorylation and apoptosis-related signals. After 24 h of drug treatment, the cells are subjected to western blot analysis. AMPK phosphorylation level is quantified by the ratio of band intensities of phospho-AMPKα vs. AMPKα.

    Dorsomorphin dihydrochloride purchased from MCE. Usage Cited in: Mol Oncol. 2017 Apr 28.

    Co-treatment of Metformin and Ribociclib induces cell death in Hep3B cells. Cells are exposed to Ribociclib at 25 μM and/or Metformin at 10 mM for 72 h.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    Dorsomorphin dihydrochloride is a potent and selective AMPK inhibitor, that is competitive with ATP, with Ki of 109±16 nM in the absence of AMP.

    IC50 & Target

    Ki: 109±16 nM (AMPK)[1]

    In Vitro

    HT1080 cells are treated with 10 μM Dorsomorphin for 2 h under 2DG stress. Immunoblot analysis reveals that phosphorylation levels of the catalytic α subunit of AMPK are increased by exposure of HT1080 cells to 2DG, whereas both basal and 2DG-induced phosphorylation levels are clearly reduced when Dorsomorphin is added. Measurements of cellular kinase activity using an ELISA-based assay system confirmed that Dorsomorphin does reduce the endogenous AMPK activity regardless of cell culture conditions[2].

    In Vivo

    Administration of Dorsomorphin over 24 h leads to a 60% increase in total serum iron concentrations. Dorsomorphin treatment is therefore effective in reducing basal levels of hepcidin expression and increasing serum iron concentrations in adult mice[3].

    References
    Preparing Stock Solutions
    Concentration Volume (DMSO) Mass 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
    Kinase Assay
    [2]

    HT1080 cells are seeded in 24-well plates (2×104 cells per well) and treated with Dorsomorphin in the presence or absence of glucose or 10 mM 2DG for 2 h. HT1080 cells that overexpressed the wild-type and dominant negative AMPKα1 are prepared by transfecting plasmid DNA (pAMPKα1-wt, pAMPKα1-D168A and pcFlag as a control) in 6-well plates, seeding in 24-well plate and treating with UPR inhibitors. Cells are lysed with cell lysis buffer (20 mM Tris-HCl, pH 7.5, 250 mM NaCl, 10% glycerol, 0.5% NP-40, 1 mM EDTA, 1 mM EGTA, 0.2 mM PMSF, 1 μg/mL pepstatin, 0.5 μg/mL leupeptin, 5 mM NaF, 2 mM Na3Vo4, 2 mM β-glycerophosphate, 1 mM DTT). Relative AMPK kinase activity (mean±SD of duplicate determinations) to control sample (vehicle or pcFlag under normal growth conditions) is determined using the CycLex AMPK kinase assay kit[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [2]

    Dorsomorphin is dissolved in DMSO (10 mM) and stored, and then diluted with appropriate media (DMSO 0.5%) before use[2].

    HeLa and 786-O cells are treated with various concentrations of Dorsomorphin (0, 0.3, 1, 3, 10 μM ), Versipelostatin and Phenformin in the presence or absence of 10 mM 2DG or 1 μg/mL of Tunicamycin as a stressor for 30 h in 96-well plates. For the combination study, 786-O cells are treated with various concentrations of UPR inhibitors in the presence or absence of 10 mM 2DG for 24 h. The medium is then replaced with fresh growth medium, and cells are cultured for a further 15 h. Subsequently, MTT is added to the culture medium, and the absorbance of each well is determined. For the viability assay under glucose-withdrawal conditions, HT1080 cells are treated with various concentrations of Dorsomorphin and phenformin in 12-well plates in the presence or absence of glucose for 18 h, seeded in 96-well plates with growth medium, and then cultured for a further 48 h before MTT is added. Relative cell survival (mean±SD of quadruplicate determinations) is calculated by setting each control absorbance from untreated cells as 100%. The effects of drug combinations at concentrations producing 80% cell growth inhibition (IC80) are analyzed using the isobologram method[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [3]

    Dorsomorphin is prepared as a stock solution in DMSO[3].

    Mice[3]
    12-week-old C57BL/6 mice raised on a standard diet are injected via the tail vein with 0.2 g/kg of Dextran or 0.2 g/kg of iron-dextran USP. Dextran is injected with vehicle only, whereas iron-dextran is injected with either vehicle or Dorsomorphin (10 mg/kg). 1 h after injection, mice are killed and liver segments are collected in 500 μL of SDS-lysis buffer and mechanically homogenized. 20 μL of liver extracts are resolved by SDS-PAGE and immunoblotted. Total RNA is harvested using Trizol from mechanically homogenized mouse livers (6 h after injection with a single intraperitoneal dose of Dorsomorphin (10 mg/kg) or DMSO). MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    M.Wt

    472.41

    Formula

    C₂₄H₂₇Cl₂N₅O

    CAS No.

    1219168-18-9

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    H2O: ≥ 48 mg/mL; DMSO: 5.2 mg/mL (Need ultrasonic)

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    Purity: 99.73%

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    Product Name:
    Dorsomorphin dihydrochloride
    Cat. No.:
    HY-13418
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