1. Epigenetics
    Cell Cycle/DNA Damage
    Autophagy
  2. HDAC
    Autophagy

Mocetinostat (Synonyms: MGCD0103; MGCD 0103; MGCD-0103)

Cat. No.: HY-12164 Purity: 99.49%
Data Sheet SDS Handling Instructions

Mocetinostat is a potent isotype-selective HDAC inhibitor with IC50 of 0.15, 0.29, 1.66 and 0.59 μM for HDAC1, HDAC2, HDAC3 and HDAC11, respectively.

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

Mocetinostat Chemical Structure

CAS No. : 726169-73-9

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10 mM * 1 mL in DMSO $55 In-stock
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50 mg $99 In-stock
100 mg $159 In-stock
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Description

Mocetinostat is a potent isotype-selective HDAC inhibitor with IC50 of 0.15, 0.29, 1.66 and 0.59 μM for HDAC1, HDAC2, HDAC3 and HDAC11, respectively.

IC50 & Target

IC50: 0.15 μM (HDAC1), 0.29 μM (HDAC2), 1.66 μM (HDAC3), 0.59 μM (HDAC11)[1]

In Vitro

Mocetinostat (MGCD0103) exhibits potent and selective antiproliferative activities against a broad spectrum of human cancer cell lines in vitro, and HDAC inhibitory activity is required for these effects. In all cell lines tested, Mocetinostat (MGCD0103) partially inhibits cellular HDAC enzyme activity although the maximal inhibition of activity varies among cell lines from 75% to 85% of total activity. The IC50 of Mocetinostat in intact cancer cells is independent of tissue origin. In A549 cells, MGCD0103 shows dose-dependent inhibition of HDAC activity in whole cells. At high concentrations in A549 cells, Mocetinostat inhibits a maximum of 80% of total activity. In HCT116 cells, Mocetinostat induces a significant S-phase depletion and both G1 and G2-M accumulation[1].

In Vivo

Mocetinostat (MGCD0103) significantly inhibits growth of human tumor xenografts in nude mice in a dose-dependent manner and the antitumor activity correlated with induction of histone acetylation in tumors. The p.o. administration of Mocetinostat (MGCD0103) (2HBr salt) significantly reduces growth of implanted advanced A549 tumors in nude mice in a dose-dependent manner after 13 days of daily administration. Mocetinostat (170 mg/kg for 2HBr salt, corresponding to 120 mg/kg of free base) significantly blocks growth of tumors compared with vehicle treatment alone (P<0.05 in post-ANOVA Dunnett's test) with no change in body weight[1].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT00511576 Mirati Therapeutics Inc. Breast Cancer|Lung Cancer|Pulmonary Cancer|Non-Small-Cell Lung Carcinoma|Prostate Cancer|Prostatic Cancer|Gastric Cancer|Stomach Cancer August 2007 Phase 1
NCT00431873 Mirati Therapeutics Inc. Lymphocytic Leukemia, Chronic January 2007 Phase 2
NCT00324194 Mirati Therapeutics Inc. Leukemia|Myelodysplastic Syndromes February 2005 Phase 1
NCT00324220 Mirati Therapeutics Inc. Myelodysplastic Syndrome|Acute Myelogenous Leukemia January 2006 Phase 1|Phase 2
NCT00358982 Mirati Therapeutics Inc. Hodgkin's Lymphoma August 2006 Phase 2
NCT00359086 Mirati Therapeutics Inc. Lymphoma August 2006 Phase 2
NCT00323934 Mirati Therapeutics Inc. Tumors|Non Hodgkin's Lymphoma April 2004 Phase 1
NCT00374296 Mirati Therapeutics Inc. Myelogenous Leukemia, Acute|Myelodysplastic Syndromes September 2006 Phase 2
NCT00324129 Mirati Therapeutics Inc. Leukemia|Myelodysplastic Syndromes February 2005 Phase 1
NCT00666497 Mirati Therapeutics Inc. Acute Myeloid Leukemia (AML)|Myelodysplastic Syndrome (MDS) June 2008 Phase 2
NCT00543582 Mirati Therapeutics Inc. Hodgkin Lymphoma|Non-Hodgkin Lymphoma (Follicular or Large Diffuse B-cell Lymphoma or Mantle Cell Lymphoma) October 2007 Phase 2
NCT00372437 Mirati Therapeutics Inc. Tumors September 2006 Phase 1|Phase 2
NCT02236195 Mirati Therapeutics Inc. Urothelial Carcinoma October 2014 Phase 2
NCT02429375 Memorial Sloan Kettering Cancer Center|MethylGene Inc. Hodgkin Lymphoma April 2015 Phase 1|Phase 2
NCT02805660 Mirati Therapeutics Inc. Advanced Cancer May 2016 Phase 1|Phase 2
NCT02993991 University Health Network, Toronto|Mirati Therapeutics Inc.|AstraZeneca Squamous Cell Carcinoma, Head And Neck|Squamous Cell Carcinoma Mouth|Resectable Squamous Cell Carcinoma of Oral Cavity January 2017 Phase 1
NCT02018926 Mirati Therapeutics Inc. Myelodysplastic Syndrome December 2013 Phase 1|Phase 2
NCT02282358 Memorial Sloan Kettering Cancer Center|MethylGene Inc. Lymphoma|Relapsed and Refractory|Diffuse Large B-Cell Lymphoma and Follicular Lymphoma October 2014 Phase 1|Phase 2
NCT02303262 Sarcoma Alliance for Research through Collaboration Metastatic Leiomyosarcoma September 2015 Phase 2
NCT03220477 Memorial Sloan Kettering Cancer Center|Merck Sharp & Dohme Corp.|Astex Pharmaceuticals|Mirati Therapeutics Inc. Lung Cancer July 2017 Phase 1
NCT02954991 Mirati Therapeutics Inc. Carcinoma, Non-Small-Cell Lung November 2016 Phase 2
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References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 2.5224 mL 12.6122 mL 25.2245 mL
5 mM 0.5045 mL 2.5224 mL 5.0449 mL
10 mM 0.2522 mL 1.2612 mL 2.5224 mL
Kinase Assay
[1]

The deacetylase enzyme assay is based on a homogeneous fluorescence release assay. Purified recombinant HDAC enzymes are incubated with Mocetinostat (MGCD0103) diluted in various concentrations for 10 min in assay buffer [25 mM HEPES (pH 8.0), 137 mM NaCl, 1 mM MgCl2, 2.7 mM KCl] at room temperature. The substrate Boc-Lys(ε-Ac)-AMC (Bachem) is added to the reaction for further incubation at 37°C. The concentration of the substrate and the incubation time varies for different isotypes of HDAC enzymes. A 20-min trypsin incubation at room temperature allows the release of the fluorophore from the deacetylated substrate. The fluorescent signal is detected by fluorometer at excitation of 360 nm, emission of 470 nm, and cutoff at 435 nm. The IC50 values of the compounds are determined by analyzing dose-response inhibition curves[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

Mocetinostat (MGCD0103) is dissolved in DMSO and stored, and then diluted with appropriate media before use[1].

Cells in 96-well plates are incubated with Mocetinostat at various concentrations for 72 h at 37°C in 5% CO2. MTT is 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)] is added. After overnight incubation, solubilized dye is quantified by reading at 570 nm using a reference at 630 nm. Absorbance values are converted to cell numbers according to a standard growth curve of the relevant cell line. The concentration which reduces cell numbers to 50% relative to DMSO-treated cells is determined as MTT IC50[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1][2]

Mocetinostat (MGCD0103) is dissolved in vehicle (PBS acidified with 0.1 N HCl or PEG400/0.2 N HCl saline, 40:60)[1].
Mocetinostat (MGCD0103) is dissolved in corn oil as suspension (Rat)[2].

Mice[1]
Female CD-1 nude mice, ages 8 to 10 wk are used. Tumor fragments (30 mg), which have been serially passaged thrice in vivo in minimal, are implanted s.c. through a small surgical incision on the flank of the mice while under general anesthesia. Mocetinostat is dissolved in vehicle (PBS acidified with 0.1 N HCl or PEG400/0.2 N HCl saline, 40:60) and dosed p.o. as solutions daily. Tumor volumes and body weight are monitored thrice weekly for at least 2 wk. Each experimental group containe six to eight animals. For pharmacokinetic study, blood is collected from animals at various time points, and plasma samples are analyzed using an Agilent 1100 HPLC system coupled with an MDS Sciex API2000 triple quadrupole mass spectrometer.
Rat[2]
Forty rats (220±20 g) are randomly divided into four different dosages of Mocetinostat groups (Low group, Medium group, High group, and control group with 10 rats in each group). Mocetinostat is dissolved in corn oil as suspension at three different concentrations (20, 40, and 80 mg/mL). Three different Mocetinostat groups (Low group, Medium group, and High group) are respectively given Mocetinostat 20, 40, and 80 mg/kg one time by intragastric administration at every morning and last for 7 days. Control group are given saline by same administration method. At 8 days morning, six probe drugs, Bupropion, Phenacetin, Tolbutamide, Metoprolol, Testosterone, and Omeprazole, are mixed in corn oil and given to the rats of three Mocetinostat groups and control group by intragastric administration at a single dosage of 10 mg/kg for Bupropion, Phenacetin, Metoprolol, Testosterone, and Omeprazole and 1 mg/kg for Tolbutamide. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
M.Wt

396.44

Formula

C₂₃H₂₀N₆O

CAS No.

726169-73-9

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

10 mM in DMSO

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

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Mocetinostat
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