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Ricolinostat

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Chemical Structure| 1316214-52-4 同义名 : ACY-1215;Rocilinostat;ACY-63
CAS号 : 1316214-52-4
货号 : A173859
分子式 : C24H27N5O3
纯度 : 99%+
分子量 : 433.503
MDL号 : MFCD22666356
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(115.34 mM)，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+40% PEG300+water 11 mg/mL clear

PO 0.5% CMC-Na 40 mg/mL suspension

生物活性
靶点

  • HDAC8

    HDAC8, IC50:100 nM

  • HDAC3

    HDAC3, IC50:51 nM

  • HDAC6

    HDAC6, IC50:4.7 nM

  • HDAC2

    HDAC2, IC50:48 nM

  • HDAC1

    HDAC1, IC50:58 nM
描述 There are 18 mammalian HDACs, HDAC 1 - 11 and sirt 1 - 7. One of the member, HDAC6 can target specific substrates like HSP90 andα-tubulin which involve in protein trafficking and degradation or cell shape and migration, thus participates in the pathways relating to neurodegenerative diseases, cancer, and immunology[1]. ACY-1215, also called Rocilinostat, is a potent and selective HDAC6 inhibitor with IC50 value of 4.7 nM (measured by HDAC enzymatic assays), while exhibits minimal inhibition on HDAC4, HDAC5, HDAC7, HDAC9, HDAC11, Sirtuin1, and Sirtuin2 (IC50 > 1 μM) and slightly inhibits HDAC8 (IC50 = 0.1 μM). A dose-dependent increased acetylatedα-tubulin and no affecting acetylation of histones can be observed in MM.1S cells with treatment of ACY-1215 for 6 hours, which confirming the selective inhibition of ACY-1215 on low dose (0.62 μM). ACY-1215 (0 - 4 μM) in combination with bortezomib (0 - 5 nM) for 24 and 48 hours in MM.1S cells and for 48 hours in RPMI8226 cells induce synergistic anti-MM activity. This may due to ACY-1215 disrupting aggresome formation with increased levels of polyubiquitinated protein, then triggers the apoptosis by the induction of ER stress and UPR. And a significant therapeutic advantage was found by combining ACY-1215 (50 mg/kg, IP) with bortezomib (0.5 mg/kg, IV) compared with either agent alone for 3 weeks, which echoes the synergistic activity cellar study[2]. ACY-1215 alone/ in combination with dexametrasone and either bortezomib or lenalidomide is currently under phase I, II clinical trials for multiple myeloma[3].
作用机制 ACY-1215 can monodentate Zn2+ of HDAC6 through its phenylhydroxamate structure[4].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
A-172 10 nM Growth Inhibition Assay 24/48 h inhibits cell growth time dependently 26150340
CCL-119 Growth Inhibition Assay 48 h IC50=1.7 μM 26116270
H9 Growth Inhibition Assay 48 h IC50=1.2 μM 26116270
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.31mL

0.46mL

0.23mL

11.53mL

2.31mL

1.15mL

23.07mL

4.61mL

2.31mL
参考文献

[1]Wang XX, Wan RZ, et al. Recent advances in the discovery of potent and selective HDAC6 inhibitors. Eur J Med Chem. 2018 Jan 1;143:1406-1418.

[2]Santo L, Hideshima T, et al. Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood. 2012 Mar 15;119(11):2579-89.

[3]Seidel C, Schnekenburger M, et al. Histone deacetylase 6 in health and disease. Epigenomics. 2015;7(1):103-18.

[4]Porter NJ, Mahendran A, et al. Unusual zinc-binding mode of HDAC6-selective hydroxamate inhibitors. Proc Natl Acad Sci U S A. 2017 Dec 19;114(51):13459-13464.

[5]Selective Inhibition of HDAC6 with a New Prototype Inhibitor (ACY-1215) Overcomes Bortezomib Resistance In Multiple Myeloma (MM)