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M344 Sale

(Synonyms: 4-(二甲氨基)-N-[7-(羟基氨基)-7-氧庚]苯甲酰胺,Histone Deacetylase Inhibitor III,MS344) 目录号 : GC16456

M344是一种组蛋白去乙酰化酶(HDAC)抑制剂,其IC50值为100nM。

M344 Chemical Structure

Cas No.:251456-60-7

规格 价格 库存 购买数量
10mM (in 1mL DMSO)
¥384.00
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1mg
¥238.00
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5mg
¥567.00
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10mg
¥886.00
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25mg
¥1,427.00
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50mg
¥2,127.00
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100mg
¥3,177.00
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Sample solution is provided at 25 µL, 10mM.

Description

M344 is a histone deacetylase (HDAC) inhibitor with an IC50 value of 100nM[1]. M344 exhibits potential for the treatment of Alzheimer's disease[2]. M344 effectively suppresses the growth and viability of various cancer cell types through multiple mechanisms[3-4].

In vitro, the addition of M344 (2.5–4μM) to HEK293 cells at 24 hours post-transfection during rAAV8 production significantly increased the genomic titer of recombinant adeno-associated virus[5]. Treatment of neuroblastoma cell lines SH-SY5Y, SK-N-BE(2), and KP-N-NS with M344 (1μM) for 12 hours markedly suppressed the mRNA and protein expression levels of c-Jun and Fra-1, while also reducing their phosphorylation activity[6].

In vivo, M344 (3–10mg/kg) was administered via intraperitoneal injection five days a week for 3-month-old Alzheimer's disease model mice for 4 months, which significantly improved their spatial memory and cognitive function[7].

References:
[1] Zhu M, Han Y, Gu T, et al. Class I HDAC inhibitors enhance antitumor efficacy and persistence of CAR-T cells by activation of the Wnt pathway. Cell Rep. 2024 Apr 23;43(4):114065.
[2] Jeong H, Shin S, Lee JS, et al. Pan-HDAC Inhibitors Promote Tau Aggregation by Increasing the Level of Acetylated Tau. Int J Mol Sci. 2019 Sep 1;20(17):4283.
[3] Yeung A, Bhargava RK, Ahn R, et al. HDAC inhibitor M344 suppresses MCF-7 breast cancer cell proliferation. Biomed Pharmacother. 2012 Apr;66(3):232-6.
[4] Knoche SM, Brumfield GL, Goetz BT, et al. The histone deacetylase inhibitor M344 as a multifaceted therapy for pancreatic cancer. PLoS One. 2022 Sep 20;17(9):e0273518.
[5] Scarrott JM, Johari YB, Pohle TH, et al. Increased recombinant adeno-associated virus production by HEK293 cells using small molecule chemical additives. Biotechnol J. 2023 Mar;18(3):e2200450.
[6] He W, Wu Y, Tang X, et al. HDAC inhibitors suppress c-Jun/Fra-1-mediated proliferation through transcriptionally downregulating MKK7 and Raf1 in neuroblastoma cells. Oncotarget. 2016 Feb 9;7(6):6727-47.
[7] Volmar CH, Salah-Uddin H, Janczura KJ, et al. M344 promotes nonamyloidogenic amyloid precursor protein processing while normalizing Alzheimer's disease genes and improving memory. Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):E9135-E9144.

M344是一种组蛋白去乙酰化酶(HDAC)抑制剂,其IC50值为100nM[1]。M344具有治疗阿尔兹海默症的潜力[2]。M344可通过多种机制对多种肿瘤细胞的增殖和活性起到抑制作用[3-4]

在体外,M344(2.5–4μM)在rAAV8生产过程中于转染后24小时添加至HEK293细胞,可显著提高重组腺相关病毒基因组滴度[5]。M344(1μM)处理神经母细胞瘤细胞系SH-SY5Y、SK-N-BE(2)及KP-N-NS 12小时,可显著抑制c-Jun与Fra-1的mRNA及蛋白表达水平,并降低其磷酸化活性[6]

在体内,M344(3–10mg/kg;每周5天)通过每日腹腔注射3月龄阿尔茨海默病模型小鼠,持续4个月,可显著改善其空间记忆与认知功能[7]

实验参考方法

Cell experiment [1]:

Cell lines

SH-SY5Y, SK-N-BE(2), and KP-N-NS cells (human neuroblastoma cell lines)

Preparation Method

Cells were maintained in DMEM supplemented with 10% fetal bovine serum (FBS). Cells were treated with M344 at a concentration of 1μM for 12 hours

Reaction Conditions

1μM; 12h

Applications

M344 significantly suppressed the mRNA and protein expression levels of both c-Jun and Fra-1, inhibition of cell growth. M344 treatment caused MKK7 downregulation at both the protein and mRNA levels.

Animal experiment [2]:

Animal models

Triple transgenic Alzheimer's disease (3xTg-AD) mice (APPsw/PS1M146v/TauP301L)

Preparation Method

Mice were intraperitoneally administered M344 at doses of 3mg/kg or 10mg/kg, 5 days per week for approximately 4 months, starting at 3 months of age (presymptomatic stage). Behavioral tests were conducted following the treatment period.

Dosage form

3 or 10mg/kg; i.p.; 5 days per week for approximately 4 months

Applications

Chronic M344 treatment significantly prevented cognitive decline. Treated mice showed improved performance in Y-maze spontaneous alternation, novel object recognition and Barnes maze spatial memory tests compared to vehicle controls. M344 treatment also significantly decreased hippocampal Aβ1-42 levels and tau phosphorylation at Ser396, while increasing ADAM10 gene expression in the hippocampus.

References:
[1] He W, Wu Y, Tang X, et al. HDAC inhibitors suppress c-Jun/Fra-1-mediated proliferation through transcriptionally downregulating MKK7 and Raf1 in neuroblastoma cells. Oncotarget. 2016 Feb 9;7(6):6727-47.
[2] Volmar CH, Salah-Uddin H, Janczura KJ, et al. M344 promotes nonamyloidogenic amyloid precursor protein processing while normalizing Alzheimer's disease genes and improving memory. Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):E9135-E9144.

化学性质

Cas No. 251456-60-7 SDF
别名 4-(二甲氨基)-N-[7-(羟基氨基)-7-氧庚]苯甲酰胺,Histone Deacetylase Inhibitor III,MS344
化学名 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]benzamide
Canonical SMILES CN(C)C1=CC=C(C=C1)C(=O)NCCCCCCC(=O)NO
分子式 C16H25N3O3 分子量 307.39
溶解度 ≥ 14.75 mg/mL in DMSO, ≥ 12.88 mg/mL in EtOH with ultrasonic 储存条件 Store at -20°C
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1 mM 3.2532 mL 16.266 mL 32.532 mL
5 mM 650.6 μL 3.2532 mL 6.5064 mL
10 mM 325.3 μL 1.6266 mL 3.2532 mL
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