 Chemical Structure.png)
M344 (D-237; MS-344), an amide analogue of Trichostatin A, is a novel and potent pan-HDAC (histone deacetylase) inhibitor with potential anticancer activity. It exhibits strong anti-proliferative activity in vitro against a variety of cancer cell lines, including MCF-7 cells, and inhibits HDAC with an IC50 of 100 nM. Moreover, it can cause cell differentiation.
Physicochemical Properties
| Molecular Formula | C16H25N3O3 | |
| Molecular Weight | 307.39 | |
| Exact Mass | 307.189 | |
| CAS # | 251456-60-7 | |
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| PubChem CID | 3994 | |
| Appearance | White to off-white solid powder | |
| Density | 1.1±0.1 g/cm3 | |
| Melting Point | 161℃ | |
| Index of Refraction | 1.558 | |
| LogP | 1.06 | |
| Hydrogen Bond Donor Count | 3 | |
| Hydrogen Bond Acceptor Count | 4 | |
| Rotatable Bond Count | 9 | |
| Heavy Atom Count | 22 | |
| Complexity | 340 | |
| Defined Atom Stereocenter Count | 0 | |
| InChi Key | MXWDSZWTBOCWBK-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C16H25N3O3/c1-19(2)14-10-8-13(9-11-14)16(21)17-12-6-4-3-5-7-15(20)18-22/h8-11,22H,3-7,12H2,1-2H3,(H,17,21)(H,18,20) | |
| Chemical Name | 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide | |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | HDAC ( IC50 = 100 nM ) | ||
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| ln Vivo |
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| Enzyme Assay | The substrate for the enzyme is chicken core histones that have been radioactively labeled. Tritium acetic acid was released by the enzyme from the substrate, and scintillation counting is used to measure it. The outcomes of triple determinations are the IC50 values. For thirty minutes, 10 μL of total [3H]acetate-prelabeled chicken reticulocyte histones (1 mg/mL) are incubated with 50 μL of maize enzyme at 30 °C. 800 μL of ethyl acetate and 36 μL of 1 M HCl/0.4 M acetate are added to stop the reaction. An aliquot of 600 μL of the upper phase is centrifuged at 10,000 g for five minutes, and its radioactivity is measured in three milliliters of liquid scintillation cocktail. M344 is examined at a 40 μM initial concentration before the active ingredients are further diluted. | ||
| Cell Assay | The MEL DS19 cells, also known as murine erythroleukemia cells, are kept in D-MEM supplemented with 10% fetal bovine serum and 100 units/mL penicillin G sodium and 100 μg/mL streptomycin sulfate at 37 °C and 5% CO2. Log-phase cells with a population doubling time of 11–13 hours are used to test M344's ability to induce cell differentiation. M344 serial dilutions are made in 24-well plates with one milliliter (mL) of D-MEM per well. The same amount of solvent (usually 2 μL/mL of medium) is present in control wells if M344 are dissolved in DMSO. Then the wells are filled with the cell suspension. The experiment is assessed after seventy-two hours. With the use of a Casy 1 TTC flow cytometer, cell counts are determined. Percentage proliferation of treated cells compared to the solvent control is used to express the proliferation. Hemoglobin is accumulated by differentiated MEL cells. According to the literature, benzidine staining thus determines the induction of cell differentiation. Add 10 μL of a 0.4% benzidine solution in 12% acetic acid with 2% H2O2 to 100 μL of cell suspension. Hemoglobin-containing cells stain blue in five minutes. The percentage of positive cells is computed by counting both benzidine-positive and -negative cells in a hemocytometer under a microscope. Initially, M344 is examined at final concentrations of 10 μM and 50 μM. For a dose-response analysis, a range of concentrations is selected based on the activity/toxicity profile. | ||
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| References |
[1]. J Med Chem . 1999 Nov 4;42(22):4669-79. [2]. Gynecol Oncol . 2006 Apr;101(1):108-13. [3]. Int J Cancer . 2007 Apr 15;120(8):1787-94. [4]. Cancer Cell Int . 2010 Sep 9:10:32. |
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| Additional Infomation |
4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide is a benzamide resulting from the formal condensation of the carboxy group of 4-(dimethylamino)benzoic acid with the amino group of 7-amino-N-hydroxyheptanamide. It is a potent inhibitor of histone deacetylases and induces cell cycle arrest and apoptosis in several human cancer cell lines. It has a role as an apoptosis inducer, an antineoplastic agent and an EC 3.5.1.98 (histone deacetylase) inhibitor. It is a member of benzamides, a hydroxamic acid, a secondary carboxamide and a tertiary amino compound. A hydroxamic acid and anilide derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used in the treatment of CUTANEOUS T-CELL LYMPHOMA and SEZARY SYNDROME. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.13 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.13 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (8.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2532 mL | 16.2660 mL | 32.5320 mL | |
| 5 mM | 0.6506 mL | 3.2532 mL | 6.5064 mL | |
| 10 mM | 0.3253 mL | 1.6266 mL | 3.2532 mL |