软木肟酸

软木肟酸用途

Suberoyl bis-hydroxamic acid (Suberohydroxamic acid; SBHA) 是竞争性且可透过细胞的 HDAC1 和 HDAC3 抑制剂,ID50 值分别为 0.25 μM 和 0.30 μM。Suberoyl bis-hydroxamic acid 使肿瘤细胞易于凋亡 (apoptosis) 并促进线粒体凋亡途径。Suberoyl bis-hydroxamic acid 可用于甲状腺髓样癌 (MTC) 的研究。

软木肟酸名称

[ CAS 号 ]:
38937-66-5

[ 中文名 ]:
软木肟酸

[ 英文名 ]:
N,N'-Dihydroxyoctanediamide

[中文别名 ]:

次异羟肟酸

[英文别名 ]:

Octanediamide, N,N-dihydroxy-
octane-1,8-dihydroxamic acid
N,N'-Dihydroxyoctanediamide
MFCD00192455

软木肟酸生物活性

[ 描述 ]:

[ 相关类别 ]:

研究领域 >> 癌症

信号通路 >> 细胞周期/DNA损伤 >> HDAC

信号通路 >> 表观遗传学 >> HDAC

[ 靶点 ]

HDAC1:0.25 μM (IC50)

HDAC3:0.30 μM (IC50)

[体外研究]

亚甲氧基双羟肟酸(10、20或50μM；24小时)与TRAIL联合使用可改善细胞凋亡程度,当TRAIL与20μM SBHA(自身仅引起10-15%的凋亡)结合时,可导致45-50%的细胞死亡[1]。单独使用亚甲酰双羟肟酸(20-50μM；10-20小时)对蛋白Bcl-xL、Mcl-1的表达几乎没有影响,但对Bax的影响较小。当它与TRAIL结合时,早期Bcl-xL和Bax的相对蛋白表达率增加,而在MM-BI和Ist-Mes2细胞中Mcl-1和Bax比值的变化在后期增加[1]。亚甲酰双羟肟酸(30μM；6小时)导致MEL细胞中乙酰化组蛋白H4的积累[2]。细胞凋亡分析[1]细胞系：MM-BI和Ist-Mes2细胞浓度：10μM、20μM或50μM孵育时间：24小时结果：细胞凋亡有协同作用。

[体内研究]

双羟肟酸亚庇罗酯(腹腔注射；200 mg/kg；每2天；12天)显示活性Notch1(NICD)显著增加,同时ASCL1降低。它能减少MTC肿瘤的生长[3]。动物模型：裸鼠注射人MTC细胞[3]剂量：200mg/kg给药：腹腔注射；每2天；12天结果：SBHA治疗组肿瘤生长抑制率平均为55%。

[参考文献]

[1]. Jiri Neuzil, et al. Sensitization of Mesothelioma to TRAIL Apoptosis by Inhibition of Histone Deacetylase: Role of Bcl-xL Down-Regulation. Biochem Biophys Res Commun. 2004 Jan 30;314(1):186-91.

[2]. V M Richon, et al. A Class of Hybrid Polar Inducers of Transformed Cell Differentiation Inhibits Histone Deacetylases.Proc Natl Acad Sci U S A

[3]. Li Ning, et al. Suberoyl Bishydroxamic Acid Activates notch1 Signaling and Suppresses Tumor Progression in an Animal Model of Medullary Thyroid Carcinoma. Ann Surg Oncol. 2008 Sep;15(9):2600-5.

软木肟酸物理化学性质

[ 密度 ]:
1.2±0.1 g/cm3

[ 熔点 ]:
153-155ºC(lit.)

[ 分子式 ]:
C₈H₁₆N₂O₄

[ 分子量 ]:
204.224

[ 精确质量 ]:
204.111008

[ PSA ]:
98.66000

[ LogP ]:
-1.81

[ 外观性状 ]:
lyophilized powder

[ 折射率 ]:
1.502

[ 储存条件 ]:
−20°C

[ 水溶解性 ]:
H2O: soluble

软木肟酸MSDS

详细MSDS(安全技术说明书)

软木肟酸安全信息

[ 安全声明 (欧洲) ]:
22-24/25

[ 危险品运输编码 ]:
NONH for all modes of transport

[ WGK德国 ]:
3

[ 海关编码 ]:
2924199090

软木肟酸合成路线

详细合成路线

软木肟酸上下游产品

软木肟酸上游产品

软木肟酸下游产品

软木肟酸海关

[ 海关编码 ]: 2924199090

[ 中文概述 ]:
2924199090. 其他无环酰胺（包括无环氨基甲酸酯)(包括其衍生物及盐）. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:30.0%

[ 申报要素 ]: 品名, 成分含量, 用途, 包装

[ Summary ]:
2924199090. other acyclic amides (including acyclic carbamates) and their derivatives; salts thereof. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

软木肟酸文献

A regimen combining the Wee1 inhibitor AZD1775 with HDAC inhibitors targets human acute myeloid leukemia cells harboring various genetic mutations.

Leukemia 29(4) , 807-18, (2015)

AZD1775 targets the cell cycle checkpoint kinase Wee1 and potentiates genotoxic agent cytotoxicity through p53-dependent or -independent mechanisms. Here, we report that AZD1775 interacted synergistic...

Reactive oxygen species, glutathione, and thioredoxin influence suberoyl bishydroxamic acid-induced apoptosis in A549 lung cancer cells.

Tumour Biol. 36 , 3429-39, (2015)

Suberoyl bishydroxamic acid (SBHA) as a histone deacetylase (HDAC) inhibitor can induce apoptosis through the formation of reactive oxygen species (ROS). However, there is no report about the regulati...

Down-Regulation of Thioredoxin1 Is Involved in Death of Calu-6 Lung Cancer Cells Treated With Suberoyl Bishydroxamic Acid.

J. Cell. Biochem. 117 , 1250-61, (2016)

Suberoyl bishydroxamic acid (SBHA), a histone deacetylase (HDAC) inhibitor, can show an anticancer effect. In this study, we investigated the effects of SBHA on the growth inhibition and death of Calu...

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