- 作用
Suberoylbis-hydroxamic酸(软木肟酸)作为第二代异羟肟酸类组蛋白去乙酰化酶抑制剂，能够抑制组蛋白去乙酰化酶中HDAC1和HDAC3的活性，小剂量、低浓度时可诱导肿瘤分化，并选择性地抑制肿瘤生长而对正常细胞无明显不良反应。通过对乳腺癌的研究发现软木肟酸呈时间、剂量依赖性抑制乳腺癌细胞增殖，使其停滞于G0～G1期。ChemicalBook
- 软木肟酸是一种组蛋白去乙酰化酶抑制剂，它可能具备激活Notch1信号通路的功能。应用Western实验检验Notch1信号通路被激活后所表达的活性蛋白NICD，来判断软木肟酸对Notch1信号通路的作用。
- 生物活性
Suberohydroxamic acid (suberic bishydroxamic acid)是竞争性HDAC抑制剂，对HDAC1和HDAC3的IC50分别为0.25 μM和0.3 μM。
- 靶点
Target
Value
HDAC1
(Cell-free assay)
0.25 μM
HDAC3
(Cell-free assay)
0.3 μM
- 体外研究
Suberoyl bis-hydroxamic acid (10, 20 or 50 μM; 24 hours) combination with TRAIL improves apoptosis extent, and when TRAIL is combined with 20 μM SBHA (itself causing only 10–15% apoptosis), resulting in 45–50% cell death.Suberoyl bis-hydroxamic acid (20-50 μM; 10-20 hours) alone has little effect on the expression of the proteins Bcl-xL, Mcl-1, and has albeit mildeffect on Bax. When it combines with TRAIL,which increases the ratio of relative protein expression of Bcl-xL and Bax in early periods, while the change in the ratio of Mcl-1 and Bax increases later in MM-BI and Ist-Mes2 cells.Suberoyl bis-hydroxamic acid (30 μM; 6 hours) causes accumulation of acetylated histone H4 in MEL cells.
Apoptosis Analysis
Cell Line:
MM-BI and Ist-Mes2 cells
Concentration:
10 μM, 20 μM or 50 μM
Incubation Time:
24 hours
Result:
Showed a cooperative effect in cell apoptosis.
- 体内研究
Suberoyl bis-hydroxamic acid (intraperitoneal injection; 200 mg/kg; every 2 days; 12 days) reveals a marked increase in the active form of Notch1 (NICD) with a concomitant decrease in ASCL1. It reduces the MTC tumor growth.
Animal Model:
Nude mice injected with human MTC cells
Dosage:
200 mg/kg
Administration:
Intraperitoneal injection; every 2 days; 12 days
Result:
Resulted in an average 55% inhibition of tumor growth in SBHA treatment group.
