Abexinostat

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Chemical Structure| 783355-60-2 同义名 : 阿贝司他 ;Pci-24781;CRA 024781;CRA-24781
CAS号 : 783355-60-2
货号 : A195616
分子式 : C21H23N3O5
纯度 : 98%+
分子量 : 397.424
MDL号 : MFCD10565969
存储条件：

Pure form Inert atmosphere,2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 3 mg/mL(7.55 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：
生物活性
靶点

  • HDAC8

    HDAC8, IC50:280 nM

  • HDAC10

    HDAC10, IC50:24 nM

  • HDAC3

    HDAC3/SMRT, Ki:8.2 nM

  • HDAC6

    HDAC6, Ki:17 nM
描述 PCI-24781 is a novel hydroxamic acid–based pan-HDAC inhibitor with Ki values of 7nM, 19nM, 8.2nM, 17nM, 280nM and 24nM for HDAC1 HDAC2, HDAC3/SMRT, HDAC6, HDAC8 and HDAC10. Treatment with PCI-24781 at concentration ranging in 0.5-10μM resulted in the accumulation of acetylated histone and acetylated tubulin in a dose-dependent manner, accompanied with increase of p21, and resulted in an inhibition of tumor cell growth and the induction of apoptosis shown by increased γH2AX and cleaved PARP in HCT116, DLD-1 and HUVEC cells. Administration of PCI-24781 (i.v., formulated in 30% HP-cyclodextrin) to mice harboring HCT116 or DLD-1 colon tumor xenografts resulted in a statistically significant reduction in tumor growth. Inhibition of HDAC enzymes by PCI-24781 led to a significant reduction in the transcription of genes specifically associated with HR, including RAD51. RAD51 protein levels were significantly decreased after 24 h of drug exposure both in vitro and in vivo.
作用机制 PCI-24781 is a hydroxamic acid–based inhibitor which can chelate the Zn2+ of HDAC.[1]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.52mL

0.50mL

0.25mL

12.58mL

2.52mL

1.26mL

25.16mL

5.03mL

2.52mL
参考文献

[1]Buggy JJ, Cao ZA, et al. CRA-024781: a novel synthetic inhibitor of histone deacetylase enzymes with antitumor activity in vitro and in vivo. Mol Cancer Ther. 2006 May;5(5):1309-17.

[2]Adimoolam S, Sirisawad M, et al. HDAC inhibitor PCI-24781 decreases RAD51 expression and inhibits homologous recombination. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19482-7. Epub 2007 Nov 27.

[3]Sholler GS, Currier EA, et al. PCI-24781 (abexinostat), a novel histone deacetylase inhibitor, induces reactive oxygen species-dependent apoptosis and is synergistic with bortezomib in neuroblastoma. J Cancer Ther Res. 2013 Dec 28;2:21.

[4]Lopez G, Liu J, et al. Combining PCI-24781, a novel histone deacetylase inhibitor, with chemotherapy for the treatment of soft tissue sarcoma. Clin Cancer Res. 2009 May 15;15(10):3472-83.