JNJ-26481585 (Synonyms: JNJ26481585) |
| Catalog No.GC15476 |
A pan-HDAC inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 875320-29-9
Sample solution is provided at 25 µL, 10mM.
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JNJ-26481585 is a novel histone deacetylase (HDAC) inhibitor that exerts a strong potency towards class I HDAC (including HDAC1, HDAC2 and HDAC3), with values of inhibition constant IC50 of 0.11, 0.33 and 4.8 nmol/L respectively, leading to strong anti-proliferative activities (IC50 ranging from 3.1 to 246 nmol/L) against a broad range of cancer cell lines including lung, breast, colon, prostate, brain and overian cancer cell lines. Recent study results have shown that JNJ-26481585 strongly induce the HDAC1-suppressed p21waf1,cip1 promoter in vivo, histone H3 acetylation in tumor tissue and apoptosis in human colon cancer cell lines (both APC wild-type and mutant) in vitro.
Reference
Arts J, King P, Mariën A, Floren W, Beliën A, Janssen L, Pilatte I, Roux B, Decrane L, Gilissen R, Hickson I, Vreys V, Cox E, Bol K, Talloen W, Goris I, Andries L, Du Jardin M, Janicot M, Page M, van Emelen K, Angibaud P. JNJ-26481585, a novel "second-generation" oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity. Clin Cancer Res. 2009;15(22):6841-6851
| Kinase experiment [1]: | |
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Inhibitory activities |
Recombinant HDAC activity assays were done by Reaction Biology Corporation. In all cases, full-length HDAC proteins were expressed using baculovirus-infected Sf9 cells. In addition, HDAC3 was coexpressed as a complex with human NCOR2. For assessing activity of HDAC1-containing cellular complexes, immunoprecipitated HDAC1 complexes were incubated with an [3H]acetyllabeled fragment of histone H4 peptide [biotin-(6-aminohexanoic)Gly-Ala-(acetyl[3H])Lys-Arg-His-Arg-Lys-Val-NH2]. Equal amounts of HDAC1 were immunoprecipitated as indicated by Western blot analysis. HDAC1 activity results are presented as mean ± SD of three independent experiments on a single lysate. |
| Cell experiment [1]: | |
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Cell lines |
Non-small cell lung carcinoma (NSCLC) cell lines; hematologic cell lines; human tumor cells; human A2780 ovarian carcinoma cells. |
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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 |
cell proliferation: 72 h, apoptosis assays: 24, 48, and 96 h. |
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Applications |
In all lung, breast, colon, prostate, brain, and ovarian tumor cell lines tested, JNJ-26481585 inhibits cell proliferation with IC50 values of 3.1-246 nM. In A2780 ovarian tumor cells, JNJ-26481585 (3-300 nM) significantly and dose-dependently increases the amount of cells positive for Annexin V, which indicates apoptosis. |
| Animal experiment [1]: | |
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Animal models |
Male athymic nu/nu CD-1 mice injected s.c. with human A2780-p21waf1,cip1 ZsGreen ovarian tumors cells |
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Dosage form |
10 mg/kg i.p. and 40 mg/kg p.o.; once daily for 3 d. |
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Preparation method |
Formulated at 2 mg/mL in 20% hydroxypropyl-β-cyclodextrin (final pH 8.7). |
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Applications |
In the HDAC1-responsive A2780 ovarian tumor screening model, JNJ-26481585 induces a bright and intense fluorescence, which is not uniformly distributed throughout the tissue and fully predicts tumor growth inhibition. Also, JNJ-26481585 induces potent H3 acetylation in the tumor tissue. In HCT116 colon xenografts, JNJ-26481585 (once daily, 10 mg/kg i.p.) for 14 days inhibits tumor volume by 76% and induces H3 acetylation. |
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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]. Arts J, King P, Marin A, et al. JNJ-26481585, a novel "second-generation" oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity. Clin Cancer Res, 2009, 15(22): 6841-6851. | |
| Cas No. | 875320-29-9 | SDF | |
| Synonyms | JNJ26481585 | ||
| Chemical Name | N-hydroxy-2-[4-[[(1-methylindol-3-yl)methylamino]methyl]piperidin-1-yl]pyrimidine-5-carboxamide | ||
| Canonical SMILES | CN1C=C(C2=CC=CC=C21)CNCC3CCN(CC3)C4=NC=C(C=N4)C(=O)NO | ||
| Formula | C21H26N6O2 | M.Wt | 394.48 |
| Solubility | ≥ 19.2 mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.535 mL | 12.6749 mL | 25.3498 mL |
| 5 mM | 0.507 mL | 2.535 mL | 5.07 mL |
| 10 mM | 0.2535 mL | 1.2675 mL | 2.535 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 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.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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