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Belinostat

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Chemical Structure| 866323-14-0 同义名 : PXD101;PX105684;brand name: Beleodaq.;NSC726630
CAS号 : 866323-14-0
货号 : A210633
分子式 : C15H14N2O4S
纯度 : 98%
分子量 : 318.34
MDL号 : MFCD08064035
存储条件：

粉末 Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(329.83 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

无水乙醇: 25 mg/mL(78.53 mM)，配合低频超声，并水浴加热至45℃助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：
生物活性
靶点

  • HDAC

    HDAC, IC50:27 nM
描述 HDACs (Histone deacetylases) 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 (HDAC11)[1]. Belinostat, also called as PXD101, is a pan-HDAC inhibitor (IC50 = 27 nM, measured by HDAC enzymatic activity)[2], inhibiting class I, II and IV HDAC isoforms with nanomolar potency[3]. Like other HDAC pan inhibitors, the hyperacetylation of H3 and H4, which are the biomarkers for the inhibition of class I HDAC, can be observed in A2780 cells treated with 1 μM belinostat for various times (0.5 - 36h). Belinostat can inhibit the growth of a number of human tumor cell lines from various origins, including A2780, HCT116, HT29, WIL, CALU-3, MCF7, PC3 and HS852 cells, with IC50 ranging 0.2 - 3.4 μM. The induction of P21 and apoptosis, as determined with measurement of PARP cleavage, by belinostat can be observed after drug incubation for 24h with concentration <1 μM in these cell lines, except for PC3 and 2780AD cell line. Belinostat shows good pharmacokinetic and pharmacodynamic properties. Treatment of belinostat 10 - 40 mg/kg daily for a week can inhibit the tumor growth of A2780 tumor-bearing mice in a dose-dependent manner, along with the increase of acetylated histone H4[2]. Co-administration of belinostat with bortezomib can synergistically induce cell death in CLL cells, which may due to the involving of other mechanism, like NF-kB inactivation and perturbation in the expression of proapoptotic and antiapoptotic proteins[4]. Belinostat was approved for the treatment of patients with relapsed or refractory PTCL. Its clinical trial of treatment for solid tumors/hematological malignancies is undergoing[5].
作用机制 The hydroxamic structure of belinostat can chelate the Zn ion of HDACs[6].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.14mL

0.63mL

0.31mL

15.71mL

3.14mL

1.57mL

31.41mL

6.28mL

3.14mL
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]Plumb JA, Finn PW, et al. Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101. Mol Cancer Ther. 2003 Aug;2(8):721-8.

[3]Sawas A, Radeski D, et al. Belinostat in patients with refractory or relapsed peripheral T-cell lymphoma: a perspective review. Ther Adv Hematol. 2015 Aug;6(4):202-8.

[4]Dai Y, Chen S, et al. Interactions between bortezomib and romidepsin and belinostat in chronic lymphocytic leukemia cells. Clin Cancer Res. 2008 Jan 15;14(2):549-58.

[5]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.

[6]New M, Olzscha H, et al. HDAC inhibitor-based therapies: can we interpret the code? Mol Oncol. 2012 Dec;6(6):637-56.

[7]Qian X, Ara G, et al. Activity of the histone deacetylase inhibitor belinostat (PXD101) in preclinical models of prostate cancer. Int J Cancer. 2008 Mar 15;122(6):1400-10.

[8]Buckley MT, Yoon J, et al. The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo. J Transl Med. 2007 Oct 12;5:49.

[9]Warren KE, McCully C, et al. Plasma and cerebrospinal fluid pharmacokinetics of the histone deacetylase inhibitor, belinostat (PXD101), in non-human primates. Cancer Chemother Pharmacol. 2008 Aug;62(3):433-7. Epub 2007 Oct 25.