Rocilinostat (ACY-1215)
(Synonyms: Ricolinostat) 目录号 : GC14998
A selective inhibitor of HDAC6
Cas No.:1316214-52-4
Sample solution is provided at 25 µL, 10mM.
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Rocilinostat (ACY-1215) is a selective inhibitor of HDAC6 with IC50 of 5 nM [1].
HDAC6 (histone deacetylase 6) is an enzyme which encoded by the HDAC6 gene and plays an important role in translational regulation, cell cycle progression and developmental events. It has been revealed that over-expression of HDAC6 is correlated with tumorigenesis and cell survival and HDAC6 also involves in cancer cells metastasis [2] [3].
Rocilinostat (ACY-1215) is a selective HDAC6 inhibitor. When tested with human MM cell lines (MM.1S), treatment with ACY-1215 in increasing dose for 6 hours increased acetylated α-tubulin at a concentration of 0.62μM via inhibiting HDAC6 [1]. In multiple myeloma cells, used ACY-125 as an adjuvant with carfilzomib triggered synergistic anti-MM effects, even in bortezomib-resistant cells which resulted in enhance cells apoptosis [2].
In mouse model with xenografted human MM cells, administration of ACY-125 only or with bortezomib could markedly delay tumor growth and the combination showed best efficacy [1].
It is also reported that ACY-1215 has minimal activity against HDAC4, HDAC5, HDAC7, HDAC9, HDAC11, Sirtuin1, and Sirtuin2 (IC50 > 1μM), and has slight activity against HDAC8 (IC50 = 0.1μM) [1]. When tested with mouse xenografted MM cells, combination carfilzomib with ACY-1215 showed a decreased effect on tumor volume and cells apoptosis [2].
References:
[1]. Santo, L., et al., Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood, 2012. 119(11): p. 2579-89.
[2]. Mishima, Y., et al., Ricolinostat (ACY-1215) induced inhibition of aggresome formation accelerates carfilzomib-induced multiple myeloma cell death. Br J Haematol, 2015.
[3]. Haakenson, J., et al., HDAC6-Dependent Functions in Tumor Cells: Crossroad with the MAPK Pathways. Crit Rev Oncog, 2015. 20(1-2): p. 65-81.
| Kinase experiment [1]: | |
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Inhibitory activities |
ACY-1215 was dissolved and subsequently diluted in assay buffer [50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA, and 20 μM tris(2-carboxyethyl)phosphine] to 6-fold the final concentration. HDAC enzymes were diluted to 1.5-fold of the final concentration in assay buffer and pre-incubated with ACY-1215 for 10 minutes before the addition of the substrate. The amount of FTS (HDAC1, HDAC2, HDAC3, and HDAC6) or MAZ-1675 (HDAC4, HDAC5, HDAC7, HDAC8, and HDAC9) used for each enzyme was equal to the Michaelis constant (Km), as determined by a titration curve. FTS or MAZ-1675 was diluted in assay buffer to 6-fold the final concentration with 0.3 μM sequencing grade trypsin. The substrate/trypsin mix was added to the enzyme/compound mix and the plate was shaken for 60 seconds and then placed into a SpectraMax M5 microtiter plate reader. The enzymatic reaction was monitored for release of 7-amino-4-methoxy-coumarin over 30 minutes, after deacetylation of the lysine side chain in the peptide substrate, and the linear rate of the reaction was calculated. HDAC11, sirtuin1, and sirtuin2 assays were performed by Cerep. |
| Cell experiment [1]: | |
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Cell lines |
MM cells; PBMCs. |
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Preparation method |
Soluble in DMSO > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reaction Conditions |
0.16, 0.8, 4, 20 nM; MM cells: 24 h, PBMCs: 48 h. |
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Applications |
ACY-1215 induces less cytotoxicity in PHA-stimulated or unstimulated PBMCs. In purified CD4+ T cells, ACY-1215 induces toxicity with IC50 value of 2.5 μM. In MM cell lines, ACY-1215 dose-dependently decreases viability with IC50 value of 2-8 μM and induces significant cytotoxicity. In MM.1S cells, ACY-1215 dose-dependently reduces DNA synthesis of MM cells adherent to BMSCs and also inhibits growth induced by IL-6 and IGF-1. |
| Animal experiment [1]: | |
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Animal models |
Male SCID mice inoculated subcutaneously with MM.1S cells. |
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Dosage form |
50 mg/kg; 5 days a week for 3 weeks; administrated orally. |
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Preparation method |
Dissolved in 10% DMSO in 5% dextrose in water |
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Applications |
In human MM xenograft mouse model, ACY-1215 (50 mg/kg) significantly delays tumor growth. Treatment mice with ACY-1215 plus bortezomib significantly prolonged overall survival (OS) and induces a significant accumulation of polyubiquitinated proteins. Treatment with ACY-1215 plus bortezomib is well tolerated and have no significant influence on the body weight. In female SCID-beige mice inoculated intravenously with MM.1S-LucNeo cells, treatment with ACY-1215 (75 mg/kg) and bortezomib (1.5 mg/kg) significantly inhibits tumor growth and prolongs OS. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Santo L, Hideshima T, Kung AL, et al. Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood, 2012, 119(11): 2579-2589. |
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| Cas No. | 1316214-52-4 | SDF | |
| 别名 | Ricolinostat | ||
| 化学名 | N-[7-(hydroxyamino)-7-oxoheptyl]-2-(N-phenylanilino)pyrimidine-5-carboxamide | ||
| Canonical SMILES | C1=CC=C(C=C1)N(C2=CC=CC=C2)C3=NC=C(C=N3)C(=O)NCCCCCCC(=O)NO | ||
| 分子式 | C24H27N5O3 | 分子量 | 433.5 |
| 溶解度 | ≥ 21.675 mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.3068 mL | 11.534 mL | 23.0681 mL |
| 5 mM | 0.4614 mL | 2.3068 mL | 4.6136 mL |
| 10 mM | 0.2307 mL | 1.1534 mL | 2.3068 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet