Ricolinostat (ACY-1215)
Catalog No.S8001 Synonyms: Rocilinostat
Molecular Weight(MW): 433.5
Ricolinostat (ACY-1215) is a selective HDAC6 inhibitor with IC50 of 5 nM in a cell-free assay. It is >10-fold more selective for HDAC6 than HDAC1/2/3 (class I HDACs) with slight activity against HDAC8, minimal activity against HDAC4/5/7/9/11, Sirtuin1, and Sirtuin2. Phase 2.
4 Customer Reviews
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(a) Representative images from hTERT RPE-1 cells transiently transfected with siControl (siC), treated with vehicle (DMSO), alisertib (MLN8237) or rocilinostat (ACY1215) at the time of serum withdrawal for 48 h. Ciliation monitored by immunofluorescent staining using acetylated α-tubulin (cilia marker) and pericentrin (basal body marker). Nuclei counterstained using DAPI. Highlighted boxes show magnified cilia. Scale bar, 3 μM.
Oncogene, 2017, 36(24):3450-3463. Ricolinostat (ACY-1215) purchased from Selleck.
Western blot analysis of PARP, C-caspase-3, total MET and phosphorylated MET (p-MET) in NuDUL-1 and Toledo cells treated as metioned. GAPDH served as a loading control. NC=negative control.
J Pathol, 2018, 246(2):141-153. Ricolinostat (ACY-1215) purchased from Selleck.
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Immunoblot of MB99-1 cells treated with the indicated compound concentrations for 48 hours. Note that the HDAC6-selective inhibitors affect tubulin acetylation, but not histone H3 acetylation, whereas the pan-HDAC inhibitor TSA increases the acetylation of both.
Mol Cancer Ther, 2015, 14(3):727-39.. Ricolinostat (ACY-1215) purchased from Selleck.
E. The expression levels of TP and TS mRNA were evaluated by qRealTime-PCR in untreated MCF-7 cells and in MCF-7 cells that were untreated or treated with selective HDACi at the indicated concentrations for 24 hours. F. The expression of TP, TS, acetylated H3 and acetylated α-tubulin proteins was determined by western blot in untreated cells and in MCF-7 cells that were treated for 48 hours with different HDACi at the indicated concentrations. α-tubulin was used as the protein loading control
Oncotarget, 2016, 7(7):7715-31. Ricolinostat (ACY-1215) purchased from Selleck.
Purity & Quality Control
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Biological Activity
| Description | Ricolinostat (ACY-1215) is a selective HDAC6 inhibitor with IC50 of 5 nM in a cell-free assay. It is >10-fold more selective for HDAC6 than HDAC1/2/3 (class I HDACs) with slight activity against HDAC8, minimal activity against HDAC4/5/7/9/11, Sirtuin1, and Sirtuin2. Phase 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Features | Induced less cytotoxicity in PHA-stimulated PBMCs from 4 healthy donors compared with the pan-HDAC inhibitor SAHA. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| In vitro |
ACY-1215 is a hydroxamic acid derivative. ACY-1215 is 12-, 10-, and 11-fold less active against HDAC1, HDAC2, and HDAC3 (class I HDACs), respectively. ACY-1215 has minimal activity (IC50 > 1μM) against HDAC4, HDAC5, HDAC7, HDAC9, HDAC11, Sirtuin1, and Sirtuin2, and has slight activity against HDAC8 (IC50 = 0.1μM). The IC50 values for ACY-1215 for T-cell toxicity is 2.5μM. ACY-1215 overcomes tumor cell growth and survival conferred by BMSCs and cytokines in the BM milieu. ACY-1215 in combination with bortezomib induces synergistic anti-MM activity. ACY-1215 induces potent acetylation of α-tubulin at very low doses and triggers acetylation of lysine on histone H3 and histone H4 only at higher doses, confirming its specific inhibitory effect on HDAC6 activity. [1] |
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| Cell Data |
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| In vivo | ACY-1215 in combination with bortezomib triggered more significant anti-MM activity than either agent alone in suppressing tumor growth and prolonging survival in both plasmacytoma model and disseminated MM model without significant adverse effects. ACY-1215 is readily absorbed by tumor tissue. Moreover, the drug does not accumulate in tumor tissue, as evidenced by the parallel decline of acetylated α-tubulin in blood cells and tumor tissue by 24 hours after dose. [1] |
Protocol
| Kinase Assay: |
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HDAC enzymatic assays: ACY-1215 is 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 are 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 is equal to the Michaelis constant (Km), as determined by a titration curve. FTS or MAZ-1675 is diluted in assay buffer to 6-fold the final concentration with 0.3μM sequencing grade trypsin. The substrate/trypsin mix is added to the enzyme/compound mix and the plate is shaken for 60 seconds and then placed into a SpectraMax M5 microtiter plate reader. The enzymatic reaction is 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 is calculated. |
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Solubility (25°C)
| In vitro | DMSO | 86 mg/mL (198.38 mM) |
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| Water | Insoluble | |
| Ethanol | Insoluble | |
| In vivo | Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 2% DMSO+30% PEG 300+ddH2O For best results, use promptly after mixing. |
5mg/mL |
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Information
| Molecular Weight | 433.5 |
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| Formula | C24H27N5O3 |
| CAS No. | 1316214-52-4 |
| Storage | powder |
| in solvent | |
| Synonyms | Rocilinostat |
Bio Calculators
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Clinical Trial Information
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
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| NCT03176472 | Not yet recruiting | Diabetic Neuropathic Pain | Regenacy Pharmaceuticals LLC | October 2018 | Phase 2 |
| NCT02856568 | Withdrawn | Non-Resectable Cholangiocarcinoma|Recurrent Cholangiocarcinoma|Stage III Extrahepatic Bile Duct Cancer|Stage III Intrahepatic Cholangiocarcinoma|Stage IIIA Hilar Cholangiocarcinoma|Stage IIIB Hilar Cholangiocarcinoma|Stage IVA Extrahepatic Bile Duct Cancer|Stage IVA Hilar Cholangiocarcinoma|Stage IVA Intrahepatic Cholangiocarcinoma|Stage IVB Extrahepatic Bile Duct Cancer|Stage IVB Hilar Cholangiocarcinoma|Stage IVB Intrahepatic Cholangiocarcinoma|Unresectable Extrahepatic Bile Duct Carcinoma | Mayo Clinic|National Cancer Institute (NCI) | May 1 2017 | Phase 1 |
| NCT02661815 | Active not recruiting | Ovarian Cancer|Fallopian Tube Cancer|Primary Peritoneal Carcinoma | Dana-Farber Cancer Institute|Celgene Corporation | June 15 2016 | Phase 1 |
| NCT02787369 | Active not recruiting | Recurrent Chronic Lymphoid Leukemia | Dana-Farber Cancer Institute|Acetylon Pharmaceuticals Incorporated | May 2016 | Phase 1 |
| NCT02632071 | Recruiting | Metastatic Breast Cancer|Breast Carcinoma | Kevin Kalinsky|Acetylon Pharmaceuticals Incorporated|National Cancer Institute (NCI)|Columbia University | February 2016 | Phase 1 |
| NCT02189343 | Active not recruiting | Multiple Myeloma | Celgene | September 15 2014 | Phase 1 |
Tech Support
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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Frequently Asked Questions
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Question 1:
What would you suggest to obtain a clear solution?
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Answer:
S8001 ACY-1215 can be dissolved in 2% DMSO/30% PEG 300/ddH2O at 5 mg/ml clearly while it in 1% DMSO/30% polyethylene glycol/1% Tween 80 at 30 mg/ml is a suspension for oral administration. Please note that the precipitation will go out from the clear solution after stayed for about half an hour, So it is recommended to prepare the solution just before use.
