Quisinostat (JNJ-26481585) 2HCl
For research use only.
Catalog No.S1096
29 publications
CAS No. 875320-31-3
Quisinostat (JNJ-26481585) 2HCl is a novel second-generation HDAC inhibitor with highest potency for HDAC1 with IC50 of 0.11 nM in a cell-free assay, modest potent to HDACs 2, 4, 10, and 11; greater than 30-fold selectivity against HDACs 3, 5, 8, and 9 and lowest potency to HDACs 6 and 7. Phase 2.
Purity & Quality Control
Choose Selective HDAC Inhibitors
Biological Activity
| Description | Quisinostat (JNJ-26481585) 2HCl is a novel second-generation HDAC inhibitor with highest potency for HDAC1 with IC50 of 0.11 nM in a cell-free assay, modest potent to HDACs 2, 4, 10, and 11; greater than 30-fold selectivity against HDACs 3, 5, 8, and 9 and lowest potency to HDACs 6 and 7. Phase 2. | ||||||||||||||||||||||||||||||||||||||||||||
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| Features | An orally bioavailable, second-generation, hydroxamic acid-based HDAC inhibitor. | ||||||||||||||||||||||||||||||||||||||||||||
| Targets |
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| In vitro |
JNJ-26481585 exhibits broad spectrum antiproliferative activity in solid and hematologic cancer cell lines, such as all lung, breast, colon, prostate, brain, and ovarian tumor cell lines, with IC50 ranging from 3.1-246 nM, which is more potent than vorinostat, R306465, panobinostat, CRA-24781, or mocetinostat in various human cancer cell lines tested. [1] A recent study shows that JNJ-26481585 promotes myeloma cell death at low nanomolar concentrations by resulting in Mcl-1 depletion and Hsp72 induction. [2] |
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| Cell Data |
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| Assay |
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| In vivo | In an HDAC1-responsive A2780 ovarian tumor screening model, JNJ-26481585 dosing at its maximal tolerated dose (10 mg/kg i.p. and 40 mg/kg p.o.) for 3 days leads to an HDAC1-regulated fluorescence , which predicts tumor growth inhibition. Furthermore, JNJ-26481585 also shows more potent inhibitory effects on the growth of C170HM2 colorectal liver metastases than 5-fluorouracil/Leucovorin. [1] |
Protocol
| Kinase Assay:[1] |
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HDAC activity assays : In all cases, full-length HDAC proteins are expressed using baculovirus-infected Sf9 cells. In addition, HDAC3 is coexpressed as a complex with human NCOR2. For assessing activity of HDAC1-containing cellular complexes, immunoprecipitated HDAC1 complexes are incubated with an [3H]acetyl- labeled fragment of histone H4 peptide [biotin-(6-aminohexanoic)Gly-Ala-(acetyl[3H])Lys-Arg-His-Arg-Lys-Val-NH2] in a total volume of 50μL enzyme assay buffer (25mM HEPES (pH 7.4), 1 M sucrose, 0.1 mg/mL BSA and 0.01% (v/v) Triton X-100). Incubation is performed for 45 minutes at 37 °C (immunoprecipitates) or 30 min at room temperature. Before addition of substrate, HDAC inhibitors are added at increasing concentrations and preincubated for 10 minutes at room temperature. After incubation, the reaction is quenched with 35μL stop buffer (1 M HCl and 0.4 M acetic acid). Released [3H]acetic acid is extracted with 800μL ethyl acetate and quantified by scintillation counting. Equal amounts of HDAC1 are immunoprecipitated as indicated by Western blot analysis. HDAC1 activity results are presented as mean ± SD of three independent experiments on a single lysate. |
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| Cell Research:Cell proliferation assays |
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| Animal Research:[1] |
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Solubility (25°C)
| In vitro | DMSO | 79 mg/mL (169.02 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 | 467.39 |
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| Formula | C21H28Cl2N6O2 |
| CAS No. | 875320-31-3 |
| Storage |
powder in solvent |
| Synonyms | N/A |
| Smiles | CN1C=C(C2=CC=CC=C21)CNCC3CCN(CC3)C4=NC=C(C=N4)C(=O)NO.Cl.Cl |
In vivo Formulation Calculator (Clear solution)
| Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment) | ||||||||||
| Dosage | mg/kg |  |
Average weight of animals | g | |
Dosing volume per animal | ul | |
Number of animals | |
| Step 2: Enter the in vivo formulation () | ||||||||||
| % DMSO % % Tween 80 % ddH2O | ||||||||||
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Calculation results:
Working concentration： mg/ml；
Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL，)
Method for preparing in vivo formulation：Take DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH2O，mix and clarify.
1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
Bio Calculators
Molarity Calculator
Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:
Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)
*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).
Dilution Calculator
Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )
* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).
Molecular Weight Calculator
Enter the chemical formula of a compound to calculate its molar mass and elemental composition:
Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2
Instructions to calculate molar mass (molecular weight) of a chemical compound:
To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
Molarity Calculator
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:
I was thinking of resuspending the powder in 10% hydroxy-propyl-β-cyclodextrin, 25mg/ml mannitol, in sterile water (final pH 8.7). Is this a good vehicle to use? What is the solubility of this chemical in such a vehicle?
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Answer:
This vehicle can be used for in vivo studies. The following papers also used this vehicle: 1. http://www.nature.com/leu/journal/v23/n10/full/leu2009121a.html; 2. http://cancerres.aacrjournals.org/content/69/13/5307.long (The solvent contains 10% hydroxypropyl-β-cyclodextrin, 0.8% HCl (0.1 N), 0.9 % NaOH (0.1 N), 3.4% mannitol and pyrogen-free water). The solubility is 2mg/ml.
