产品说明书

Pracinostat

Print
Chemical Structure| 929016-96-6 同义名 : SB939
CAS号 : 929016-96-6
货号 : A477591
分子式 : C20H30N4O2
纯度 : 99%+
分子量 : 358.478
MDL号 : MFCD17215206
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 250 mg/mL(697.39 mM)，配合低频超声助溶，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
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 10 mg/mL clear

PO 0.5% CMC-Na 38 mg/mL suspension

生物活性
靶点

  • HDAC8

    HDAC8, IC50:140 nM

  • HDAC10

    HDAC10, IC50:40 nM

  • HDAC3

    HDAC3, IC50:43 nM

  • HDAC4

    HDAC4, IC50:56 nM
描述 HDACs are a group of enzymes that remove acetyl groups and regulate the histone tail, protein-DNA interaction, chromatin conformation, and even transcription. There are 18 mammalian HDACs divided into four classes: class I (HDACs 1, 2, 3, 8), class II (HDACs 4, 5, 6, 7, 9, 10), class III (sirtuin family: sirt1-sirt7) and class IV (HDAC 11)[1]. Pracinostat (SB-939) is identified as a potent hydroxamate-based inhibitor of class I, II and IV HDACs, inhibiting the isolated enzymes with IC50 values of 43 to 140 nM, 40 to 137 nM (class II), and 93 nM (class IV) with the exception of HDAC6. Pracinostat is effective on cell proliferation of various kinds of human cancer cell lines, including T-cell lymphoma cells and leukemia cells with IC50 values ranging from 50 nM to 170 nM, colon and prostate cancer cell lines with IC50 values ranging from 340 to 540 nM. However, no inhibition of the proliferation of normal human dermal fibroblasts at concentrations up to 100 μM can be observed. Treatment of pracinostat >0.125 μM can induce ac-H3 and the acetylation of α-tubulin in HCT-116 cells after 24h. Meanwhile, pracinostat >0.25 μM leads to decreased retinoblastoma serine phosphorylation on S807/811 and an increase of the cyclin-dependant kinase inhibitor p21Cip/WAF. Echoed to that, the increase in cell cycle arrest goes hand in hand with a dose-dependent increase of PARP. In animal study, a single dose of either 50 or 125 mg/kg of pracinostat causes increased ac-H3 in the tumor tissue of HCT-116 xenografted nude mice. Oral treatment of pracinostat once a day for 21 days, on dose of 100 mg/kg, achieves 94% tumor growth inhibition. These results show the superior pharmacokinetic and pharmacodynamic properties of pracinostat in in vivo study[2]. A phase 3 study of pracinostat in combination with azacitidine in adults with acute myeloid leukemia and a phase 2 study of pracinostat with azacitidine in patients with previously untreated myelodysplastic syndrome can be seen (https://www.cancer.gov/).
作用机制 Pracinostat is an hydroxamate-based HDAC inhibitor, structure of which can chelate Zn ion of HDACs.
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
HCT116 cells Proliferation assay 48 h Antiproliferative activity against human HCT116 cells after 48 hrs by sulforhodamine B assay, GI50=0.24 μM 24119555
MCF7 cells Proliferation assay 48 h Antiproliferative activity against human MCF7 cells after 48 hrs by sulforhodamine B assay, GI50=0.17 μM 24119555
MDA-MB-435 cells Proliferation assay 48 h Antiproliferative activity against human MDA-MB-435 cells after 48 hrs by sulforhodamine B assay, GI50=0.48 μM 24119555
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.79mL

0.56mL

0.28mL

13.95mL

2.79mL

1.39mL

27.90mL

5.58mL

2.79mL
参考文献

[1]Yoon S, Eom GH, et al. HDAC and HDAC Inhibitor: From Cancer to Cardiovascular Diseases. Chonnam Med J. 2016 Jan;52(1):1-11.

[2]Novotny-Diermayr V, Sangthongpitag K, et al. SB939, a novel potent and orally active histone deacetylase inhibitor with high tumor exposure and efficacy in mouse models of colorectal cancer. Mol Cancer Ther. 2010 Mar;9(3):642-52.

[3]Mottamal M, Zheng S, et al. Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents. Molecules. 2015 Mar 2;20(3):3898-941.

[4]Wang H, Yu N, et al. Discovery of (2E)-3-{2-butyl-1-[2-(diethylamino)ethyl]-1H-benzimidazol-5-yl}-N-hydroxyacrylamide (SB939), an orally active histone deacetylase inhibitor with a superior preclinical profile. J Med Chem. 2011 Jul 14;54(13):4694-720.