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M344

Cat. No. M3395
M344 Structure
Synonym:

D 237; MS 344

Size Price Availability Quantity
5mg USD 60  USD60 In stock
10mg USD 95  USD95 In stock
50mg USD 420  USD420 In stock
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Quality Control & Documentation
Biological Activity

M344 shows a potent inhibition activity against histone deacetylase with IC50 of 100 nM. M344 produces a more significant effect on cell proliferation than on cell differentiation in MEL DS19 cells. M344 shows cell toxicity at concentrations above 10 μM, while a maximum of only 20% of the surviving cell population are induced to differentiate. In vitro, M344 produces the significant anti-proliferative effects on the endometrial cancer cell line Ishikawa and the ovarian cancer cell line SK-OV-3 with EC50 of 2.3 μM and 5.1 μM, respectively. While the normal human endometrial epithelial cells shows little sensitivity to M344. In addition, M344 also decreases proportion of cells in the S-phase, increases proportion in the G0/G1 phases of the cell cycle, induces apoptosis and decreases the transmembrane potential of mitochondria. M344 show the anti-proliferative activities against embryonal nervous system tumor cells including medulloblastoma cells (D341 Med, Daoy) and neuroblastoma cells (CH-LA 90,SHSY-5Y ) with GI50 of 0.65 μM, 0.63 μM, 0.63 μM and 0.67 μM, respectively.M344 (5 μM ) in combination with cisplatin (10 μg/mL) results increased induction of ATF3 and shows enhanced cytotoxic effects than cisplatin alone in a panel of human derived cancer cell lines, such as MCF-7, PC3, SK-OV3, and A549.

Customer Product Validations & Biological Datas
Source Cell Death Dis (2018). Figure 1. M344
Method cell viability assay
Cell Lines T-ALL cells
Concentrations 1 μM
Incubation Time 24 and 48 h
Results Compared with the single treatment (Fig. 1a–c), the combination of vorinostat and QC significantly decreased cell viability.
Protocol (for reference only)
Cell Experiment
Cell lines MEL DS19 cells
Preparation method Maintaining MEL DS19 cells (murine erythroleukemia cells) in D-MEM containing 100 units/mL penicillin G sodium and 100 μg/mL streptomycin sulfate supplemented with 10% fetal bovine serum at 37 °C in a 5% CO2 atmosphere. To test M344 for potential to induce cell differentiation, log-phase cells with a population doubling time of 11−13 hours are used. Preparing Serial dilutions of M344 in 24-well plates using 1 mL of D-MEM/well. If M344 are dissolved in DMSO, control wells contains the same amount of solvent (generally 2 μL/mL of medium). Subsequently, adding the cell suspension to the wells. After 72 hours the experiment is evaluated. Using a Casy 1 TTC flow cytometer to counte cell numbers. With the solvent control , expressing the proliferation of treated cells as percent proliferation in comparison. Differentiated MEL cells accumulate hemoglobin. Therefore, the induction of cell differentiation is determined by benzidine staining according to the literature. To 100 μL of cell suspension is added 10 μL of a 0.4% solution of benzidine in 12% acetic acid which contains 2% H2O2. Within 5 minutes hemoglobin-containing cells stains blue.Under the microscope in a hemocytometer ,counting Benzidine-positive and -negative cells , and calculating the percentage of positive cells . Testing M344 first at 10 μM and 50 μM final concentration. A range of concentrations is chosen for a dose−response analysis according to activity/toxicity profile,.
Concentrations 0 to 50 μM
Incubation time 72 hours
Animal Experiment
Animal models
Formulation
Dosages
Administration
Chemical Information
Molecular Weight 307.39
Formula C16H25N3O3
CAS Number 251456-60-7
Solubility (25°C) DMSO 55 mg/mL
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 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 Compound A of 10 mg/kg.

References

[1] Claude-Henry Volmar, et al. M344 promotes nonamyloidogenic amyloid precursor protein processing while normalizing Alzheimer's disease genes and improving memory

[2] L Jin, et al. Histone deacetylase inhibitor M344 significantly improves nuclear reprogramming, blastocyst quality, and in vitro developmental capacity of cloned pig embryos

[3] No authors listed. Gynecol Oncol. Retraction notice to "M344 is a novel synthesized histone deacetylase inhibitor that induces growth inhibition, cell cycle arrest, and apoptosis in human endometrial cancer and ovarian cancer cells" [Gynecol. Oncol. 101 (2006) 108-113]

[4] Angie Yeung, et al. HDAC inhibitor M344 suppresses MCF-7 breast cancer cell proliferation

[5] Noriyuki Takai, et al. M344 is a novel synthesized histone deacetylase inhibitor that induces growth inhibition, cell cycle arrest, and apoptosis in human endometrial cancer and ovarian cancer cells

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Keywords: M344, D 237; MS 344 supplier, HDAC, inhibitors, activators


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