M344

M 344 is an inhibitor of histone deacetylases (HDACs), inhibiting maize HDAC (IC50 = 100 nM) as well as human HDAC1 (IC50 = 46 nM). It shows a three-fold selectivity for inhibition of HDAC6 over HDAC1. M 344 enhances the sensitivity of human squamous carcinoma cells to radiation and promotes cell cycle arrest and apoptosis in human endometrial cancer and ovarian cancer cells (ED50 = 2.3 μM).

Histone deacetylase inhibitor III. A cell-permeable amide analog of Trichostatin A that potently inhibits HDACs.

ChEBI: 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 cell-permeable amide analog of Trichostatin A (Cat. No. 647925) that potently inhibits histone deacetylases (IC₅₀ = 40 nM for rat liver HDAC and IC₅₀ = 100 nM for maize HD). Induces differentiation and inhibits proliferation (~2 μM) of murine erythroleukemia cells.

Histone deacetylase inhibitor (IC 50 = 100 nM). Induces terminal cell differentiation and causes an increase in hyperacetylated histone H4. Antiproliferative agent; suppresses the growth of human endometrial and ovarian cancer cells by inducing cell cycle arrest and apoptosis.

Cell permeable: yes

M344 is a small-molecule histone deacetylase (HDAC) inhibitor with potent inhibitory activity against class I (HDAC 1, 2, 3, 8) and class IIb (HDAC 6, 10) HDACs. Employing an epigenetic approach, it can simultaneously affect the expression of multiple AD-related genes, thereby counteracting the polygenic nature of Alzheimer's disease (AD).

M344 can regulate secretase and APP processing, reduce Aβ and improve related genes. Compared with other HDAC inhibitors, M344 showed better safety in experiments and had no negative impact on cell viability.

[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.
[5] Volmar, C.-H., Salah-Uddin, H., Janczura, K. J., Halley, P., Lambert, G., Wodrich, A., Manoah, S., Patel, N. H., Sartor, G. C., Mehta, N., Miles, N. T. H., Desse, S., Dorcius, D., Cameron, M. D., Brothers, S. P., &amp; Wahlestedt, C. (2017). M344 promotes nonamyloidogenic amyloid precursor protein processing while normalizing Alzheimer’s disease genes and improving memory. <i>Proceedings of the National Academy of Sciences of the United States of America</i>, <i>114 43</i>, E9135–E9144. https://doi.org/10.1073/pnas.1707544114