Quisinostat 2HCl
产品说明书
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同义名 : | JNJ-26481585 dihydrochloride;Quisinostat dihydrochloride |
| CAS号 : | 875320-31-3 | |
| 货号 : | A562597 | |
| 分子式 : | C21H28Cl2N6O2 | |
| 纯度 : | 99+% | |
| 分子量 : | 467.392 | |
| MDL号 : | MFCD29905457 | |
| 存储条件： |
Pure form Inert atmosphere,2-8°C In solvent -20°C:3-6个月-80°C:12个月 |
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| 溶解度 : |
DMSO: 30 mg/mL(64.19 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO |
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| 动物实验配方： |
IP 2% DMSO+water 7 mg/mL clear PO 0.5% CMC-Na 40 mg/mL suspension |
| 生物活性 | |||
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| 靶点 |
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| 描述 | The inhibition of HDACs increases the acetylation of histone proteins, which affects the tertiary chromatin structure and leads to altered expression of genes involved in cell proliferation, apoptosis and differentiation. Thus, it makes a key role for inhibition of HDACs in anti-proliferation of tumor cells. Quisinostat is an oral pan-HDAC inhibitor with highest potency for HDAC1 (IC50=0.11±0.03nM, measured by recombinant HDAC enzyme activity), modest potent to HDAC 2, 4, 10 and 11nM and a lower potency on the rest HDACs. Increased level of acetylated histone H3 (H3 Ac), H4 (H4 Ac), histone H4-acetyl K16 (H4-K16 Ac) and histone H4-trimethyl K20 (H4-K20Me3) (acetylation regulated by HDAC1-3), p21 and E-cadherin (expression regulated by HDAC1), as well as increased tubulin acetylation, induction of Hsp70, and loss of Hsp90 client c-Raf can be observed in a dose-dependent manner (30-1000nM) after 24-hour treatment with Quisinostat in human A2780 ovarian carcinoma cells, which shows activity against pan-HDAC inhibition. Also, Quisinostat can inhibit cell growth in all lung, breast, colon, prostate, brain, and ovarian tumor cell lines tested with IC50 values ranging from 3.1 to 246nM, which shows its antiproliferative effect in a broad panel of human tumor cell lines from both solid and hematologic origin. Compared with the first generation of HDAC inhibitors (SAHA or TSA), Quisinostat shows prolonged pharmacodynamic response in vivo. Quisinostat can induce continuous H3 acetylation in tumor tissue from A2780 ovarian tumor-bearing nude mice when treated with Quisinostat at 10mg/kg as well as increased level of HDAC1-regulated p21[1]. Up to now, a phase I study of Quisinostat in patients with advanced solid tumors has been done[2]. | ||
| 作用机制 | Quisinostat is a pyrimidyl-hydroxamic acid analogue, which can chelate the Zn2+ ion of HDAC. [1] | ||
| 实验方案 | |||
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| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
2.14mL 0.43mL 0.21mL |
10.70mL 2.14mL 1.07mL |
21.40mL 4.28mL 2.14mL |
