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

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

Cat. No.: HY-13418 Purity: 99.73%
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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10 mM * 1 mL in Water USD 66 In-stock
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Other Forms of Dorsomorphin dihydrochloride:

    Dorsomorphin dihydrochloride purchased from MCE. Usage Cited in: Biochem Pharmacol. 2016 Dec 15;122:42-61.

    Inhibition of SREBPs processing by AHI is dependent on LKB-1/AMPK/mTOR pathway. (A) HepG2 cells are incubated with or without MHY1485 or Rapamycin for 1 h, the cells are switched to medium D in the presence of vehicle, or AHI. (B) HepG2 cells are incubated with or without Compound C for 1 h, the cells are switched to medium D in the presence of vehicle, or AHI.

    Dorsomorphin dihydrochloride purchased from MCE. Usage Cited in: Int J Mol Sci. 2017 May 19;18(5). pii: E1063.

    Inhibition of sirt1 and AMPK blocked Rb2-induced hepatic autophagy. HepG2 cells are pretreated with 50 µM Rb2 for 4 h in the presence or absence of the sirt1 inhibitor EX-528 (EX) and the specific AMPK inhibitor Compound C (CC), and then subjected to OA (1 mM for HepG2 and 2 mM for primary mouse hepatocytes) exposure for 12 h. For lipid content determination, intracellular TG are stained by Oil red O (ORO). ORO is then eluted with isopropanol and the optical absorbance of the eluate is measured

    Dorsomorphin dihydrochloride purchased from MCE. Usage Cited in: Free Radic Biol Med. 2016 Nov 9;101:401-412.

    Effect of EsA on AMPK activation is necessary for AKT/GSK3β-mediated Nrf2 activity and cytoprotection. Cells are treated with 3 μM Compound C for 18 h, followed by treatment with EsA for 6 h, and then cell lysates are immunoblotted to assess the phosphorylation of AMPK, Akt and GSK3β and Nrf2.

    Dorsomorphin dihydrochloride purchased from MCE. Usage Cited in: Oncotarget. 2016 Apr 5;7(14):18085-94.

    MACC1 is up-regulated by ACh through p-AMPK. A. ACh stimulates AMPK phosphorylation via M3R. B. Inhibition of AMPK activity by Dorsomorphin (8 μM) suppresses the induction of MACC1 expression by ACh. p-AMPK levels increase after ACh stimulation, and pretreatment of Darifenacin attenuates the ACh-induced increase of p-AMPK.

    Dorsomorphin dihydrochloride purchased from MCE. Usage Cited in: Cell Death Dis. 2017 May 18;8(5):e2798.

    Involvement of the AMPK/AKT/GSK3β pathway in Nrf2 nuclear translocation by Betulin. Cells are treated with 3 μM compound C (Comp.C) for 18 h before treatment with betulin (36 μM) for 6 h. Cell lysates are immunoblotted for the phosphorylation of AMPK, Akt, GSK3β and Nrf2.

    Dorsomorphin dihydrochloride purchased from MCE. Usage Cited in: Am J Chin Med. 2017 Aug 22:1-17.

    Activity of MMP-2 and MMP-9 in water extract (WAF)- and ethanol extract (EtAF)-treated CT26 cells after CC (20 μM) pretreatment for 4 h.

    Dorsomorphin dihydrochloride purchased from MCE. Usage Cited in: Mol Cell. 2017 Oct 19;68(2):336-349.e6.

    AMPK DKO SV40-immortalized MEFs are electroporated with plasmids encoding Myc-tagged AMPK α1, Myc-tagged AMPK α2 and Myc-tagged AMPK α2 S > A. 48 hr later, MEFs are starved for 3 hr and treated for 2 hr with DMSO or 50 mM A769662 before protein extraction. Western blot analysis shows the A769662-induced ACC phosphorylation in transfected cells.

    Dorsomorphin dihydrochloride purchased from MCE. Usage Cited in: Zhongguo Sheng Wu Hua Xue Yu Fen Zi Sheng Wu Xue Bao. 2017;8,33(8):781-788.

    Western blotting for AMPKα, p-AMPKα and CCS.C13 cells are exposed to 10 μM Compound C 12 hours. The cell lysates are prepared and AMPKα, p-AMPKα and CCS are examined by Western blotting with specific antibodies. The data are representative of three independent experiments.

    Dorsomorphin dihydrochloride purchased from MCE. Usage Cited in: Biomed Pharmacother. 2018 Feb 19;100:417-425.

    HaCaT cells are pre-incubated with Compound C (CC) (10 μM) and U0126 (10 μM), pharmacological inhibitors of AMPKα, ERK, respectively, for 1 h before treatment with DA8 and DA14 (DAs).

    Dorsomorphin dihydrochloride purchased from MCE. Usage Cited in: Front Pharmacol. 2018 Feb 5;9:68.

    CT26 cells are treated with CC for 4 h and detected phosphorylation levels of AMPK.

    Dorsomorphin dihydrochloride purchased from MCE. Usage Cited in: Biotechnol Appl Biochem. 2018 Mar 25.

    The mTOR inhibitor Rapamycin augments the autophagy induced by GEM. (A, B) Beclin-1 and LC3B expression is analyzed by western blot after treatment of the cells with GEM (5 μM) and Rapamycin (0, 1, and 2.5 μM) for 48 (A) or 72 (B) h.

    Dorsomorphin dihydrochloride purchased from MCE. Usage Cited in: Redox Biol. 2018 Apr 18;17:180-191.

    MDA-MB-231 cells are cultured in poly-HEMA coated dishes and treated with Compound C or GL-V9 for 36 h. The expression of AMPK and p-AMPK in Compound C treated cells are assayed by Western blotting.
    • 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[1]

    AMPK

    109 nM (Ki)

    Autophagy

     

    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].

    Clinical Trial
    References
    Preparing Stock Solutions
    Concentration Volume 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
    Please refer to the solubility information to select the appropriate solvent.
    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
    Molecular Weight

    472.41

    Formula

    C₂₄H₂₇Cl₂N₅O

    CAS No.

    1219168-18-9

    SMILES

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

    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)

    Dorsomorphin dihydrochloride is dissolved in saline[4].

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

    References

    Purity: 99.73%

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