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M344

In stock
Catalog No.
A4105
HDAC inhibitor,potent and cell-permeable
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$55.00
In stock
Evaluation Sample
$28.00
In stock
5mg
$50.00
In stock
50mg
$360.00
In stock

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M344 is a potent inhibitor of HDAC with IC50 value of 100 nM and enable the induction of cell differentiation [1].

Treatment with M344 for 1 or 3 days induced a decreased relative p53 mRNA level and increased p21waf1/cip1 mRNA expression while no change in p53 protein. The result demonstrated the independent of p53 of inhibitory effects of M344 on MCF-7 cell growth. And the increased expression of the pro-apoptotic Puma, which can be induced by p53-independent pathways, is in accordance with the suppression of MCF-7 cell growth observed after the M344 treatment. On the other hand, M344 also show the ability in increasing the response to radiation in SCC-35 and SQ-20B human squamous carcinoma lines [2].

In MEL DS19 cells, M344 shows a much more significant effect on cell proliferation than the effect on cell differentiation. M344 exhibits toxic at concentrations of above 10 μM, when only 20% of the surviving cell population at most are induced to differentiate. M344 significantly inhibits proliferation of embryonic nervous system tumor cells, including medulloblastoma cells (D341 MED) with GI50 value of 0.65 μM and neuroblastoma cells (CH-LA 90) with GI50 value of 0.63 μM [1, 3].

M344 also plays an important role in the modification of histone and transcription factor of NF- kB in regulating HIV-1 LTR gene expression, showing the potential anti-latency therapies. Experiments were carried out in the cells, which latently infected Jurkat cells encoding the green fluorescence protein (GFP) under control of the HIV-1 LTR that act as a marker of expression of HIV-1 LTR, 72 hours after treatment with 200 nM M344, expression of HIV-1 activity was found, and the percentage of GFP-expressing cells was detected as high as 25.2% more than the cells which was subjected to mock treatment [4].

References:
[1].  Jung M, Brosch G , Kolle D, et al. Amide analogues of trichostatin A as inhibitors of histone deacetylase and inducers of terminal cell differentiation. JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (22): 4669-4679.
[2].  Yeung A, Bhargava RK, Ahn, R, et al. HDAC inhibitor M344 suppresses MCF-7 breast cancer cell proliferation. BIOMEDICINE & PHARMACOTHERAPY, 2012, 66 (3): 232-236.
[3].  Furchert SE, Lanvers-Kaminsky C , Jurgens H , et al. Inhibitors of histone deacetylases as potential therapeutic tools for high-risk embryonal tumors of the nervous system of childhood. INTERNATIONAL JOURNAL OF CANCER, 2007, 120 (8): 1787-1794.
[4].  Ying H, Zhang YH , Zhou X , et al. Selective Histonedeacetylase Inhibitor M344 Intervenes in HIV-1 Latency through Increasing Histone Acetylation and Activation of NF-kappaB. PLOS ONE, 2012, 7 (11): e48832.

Product Citation

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt307.39
Cas No.251456-60-7
FormulaC16H25N3O3
SynonymsHistone Deacetylase Inhibitor III,MS344
Solubility≥14.75 mg/mL in DMSO, ≥12.88 mg/mL in EtOH with ultrasonic, <2.5 mg/mL in H2O
Chemical Name4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide
SDFDownload SDF
Canonical SMILESCN(C)C1=CC=C(C=C1)C(=O)NCCCCCCC(=O)NO
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Protocol

Cell experiment [1]:

Cell lines

MCF-7 breast cancer cell line

Preparation method

The solubility of this compound in DMSO is > 14.75 mg/ml. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

1 μM to 100 μM for 1–7 days

Applications

Bonferroni posthoc analysis indicated that treatment of MCF-7 cells with M344 for 1 day caused a significant inhibition at 50 μM, whereas treatment for 3 days showed significant inhibition at 10 μM, 50 μM and 100 μM, with a maximal inhibition of 40% at 100 μM. After 5 days, all concentrations of M344 caused a significant suppression of MCF-7 cell growth, with a maximal inhibition of 60% observed at 10 μM.

Ex-vivo animal experiment [2]:

Animal models

Brain slice from 5-day-old Wistar rats

Dosage form

Submicromolar doses

Application

Suberoylanilide hydroxamic acid (SAHA) increased survival motor neuron (SMN) levels in several neuroectodermal tissues, including rat hippocampal brain slices and motoneurone-rich cell fractions. SAHA activated survival motor neuron gene 2 (SMN2) and inhibited HDACs at submicromolar doses. In contrast to SAHA, M344 displayed unfavourable toxicity profiles.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Yeung A, Bhargava RK, Ahn, R, et al. HDAC inhibitor M344 suppresses MCF-7 breast cancer cell proliferation. BIOMEDICINE & PHARMACOTHERAPY, 2012, 66 (3): 232-236.

[2] Hahnen E et al. In vitro and ex vivo evaluation of second-generation histone deacetylase inhibitors for the treatment of spinal muscular atrophy. J Neurochem. 2006 Jul;98(1):193-202.

Biological Activity

Description M344 is a potent inhibitor of HDAC with IC50 of 100 nM and able to induce cell differentiation.
Targets HDAC          
IC50 100 nM          

Quality Control

Chemical structure

M344

Related Biological Data

M344

Related Biological Data

M344

Related Biological Data

M344
 

Research Update

1. Selective histonedeacetylase inhibitor M344 intervenes in HIV-1 latency through increasing histone acetylation and activation of NF-kappaB. PLoS One. 2012;7(11):e48832. doi: 10.1371/journal.pone.0048832. Epub 2012 Nov 15.
Abstract
The effects and mechanism of M344, a HDAC inhibitor with robust anticancer activity and low toxicity, on inducing HIV expression in latently infected cells are yet to be explored.
2. HDAC inhibitor M344 suppresses MCF-7 breast cancer cell proliferation. Biomed Pharmacother. 2012 Apr;66(3):232-6. doi: 10.1016/j.biopha.2011.06.007. Epub 2011 Aug 27.
Abstract
M344 is an HDAC inhibitor that concentrate- and time-dependently decreases proliferation, reduces p53 mRNA expression without affecting p53 protein levels and induces expression of Puma and Bax with morphological features of apoptosis in MCF-7 breast cancer cells.
3. A pediatric phase 1 trial of vorinostat and temozolomide in relapsed or refractory primary brain or spinal cord tumors: a Children's Oncology Group phase 1 consortium study. Pediatr Blood Cancer. 2013 Sep;60(9):1452-7. doi: 10.1002/pbc.24541. Epub 2013 Mar 28.
Abstract
The combination of vorinostat and temozolomide has been evaluated for MTD, DLT and pharmacokinetic properties in children with refractory or recurrent CNS malignancies.
4. Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study. Lancet Oncol. 2013 Oct;14(11):1129-40. doi: 10.1016/S1470-2045(13)70398-X. Epub 2013 Sep 19.
Abstract
The combination of vorinostat and bortezomib has been assessed for efficacy and tolerability in patients with relapsed or refractory multiple myeloma.