MGCD0103 (Mocetinostat) is a novel HDAC inhibitor, highly specific for classes I and IV HDACs. It is well-tolerated and exhibits favorable pharmacokinetic and pharmacodynamic profiles, demonstrating target inhibition and clinical responses. MGCD0103 (Mocetinostat) has been recently shown to exhibit various effects on non-histone targets on cancer cells. The latest preclinical studies have demonstrated that MGCD0103 can induce both cell death and autophagy.
|Source||Int J Clin Exp Pathol (2015). Figure 3. MGCD0103|
|Cell Lines||liver cells|
|Concentrations||20, 40, 80 mg/kg|
|Incubation Time||7 days|
|Results||According to the pathological changes of liver at difference dosage, MGCD0103 is hepatotoxic and its toxity is dosedependent.|
|Cell lines||HCT116, HCT15, HT29, DU145, MDA-mb231, A549 cells line|
|Preparation method||Cell Viability Assay
Cells in 96-well plates were incubated with compounds at various concentrations for 72 h at 37°C in 5% CO2. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT; Sigma) was added at a final concentration of 0.5 mg/mL and incubated with the cells for 4 h before an equal volume of solubilization buffer [50% N,N-dimethylformamide, 20% SDS (pH 4.7)] was added. After overnight incubation, solubilized dye was quantified by reading at 570 nm using a reference at 630 nm. Absorbance values were converted to cell numbers according to a standard growth curve of the relevant cell line. The concentration which reduced cell numbers to 50% relative to DMSO-treated cells was determined as MTT IC50.
|Concentrations||0~100 μ M|
|Incubation time||72 h|
|Animal models||Female CD-1 nude mice|
|Formulation||PBS acidified with 0.1 N HCl or PEG400/0.2 N HCl saline, 40:60|
|Dosages||daily for at least 2 weeks|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
Mocetinostat (MGCD0103): a review of an isotype-specific histone deacetylase inhibitor.
Boumber Y, et al. Expert Opin Investig Drugs. 2011 Jun;20(6):823-9. PMID: 21554162.
Histone deacetylase inhibitor MGCD0103 synergizes with gemcitabine in human pancreatic cells.
Sung V, et al. Cancer Sci. 2011 Jun;102(6):1201-7. PMID: 21375679.
The class I HDAC inhibitor MGCD0103 induces cell cycle arrest and apoptosis in colon cancer initiating cells by upregulating Dickkopf-1 and non-canonical Wnt signaling.
Sikandar S, et al. Oncotarget. 2010 Nov;1(7):596-605. PMID: 21317455.
Epigenetic modulation of MAGE-A3 antigen expression in multiple myeloma following treatment with the demethylation agent 5-azacitidine and the histone deacetlyase inhibitor MGCD0103.
Moreno-Bost A, et al. Cytotherapy. 2011 May;13(5):618-28. PMID: 21171821.
The class-I HDAC inhibitor MGCD0103 induces apoptosis in Hodgkin lymphoma cell lines and synergizes with proteasome inhibitors by an HDAC6-independent mechanism.
Buglio D, et al. Br J Haematol. 2010 Nov;151(4):387-96. PMID: 20880107.
The histone deacetylase inhibitor MGCD0103 has both deacetylase and microtubule inhibitory activity.
Chia K, et al. Mol Pharmacol. 2010 Sep;78(3):436-43. PMID: 20538840.
MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo.
Fournel M, et al. Mol Cancer Ther. 2008 Apr;7(4):759-68. PMID: 18413790.
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