AR-42 (OSU-HDAC42) |
| Catalog No.GC14590 |
HDAC inhibitor,novel and potent
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 935881-37-1
Sample solution is provided at 25 µL, 10mM.
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AR-42 (also known as OSU-HDAC42), a derivative of hydroxamate-tethered phenylbutyrate, is a novel and potent inhibitor of histone deacetylase (HDAC) that potently inhibits the activity of HDAC with 50% inhibition concentration IC50 value of 16 nM and induces histone H3 acetylation, α-tubulin acetylation and p21 up-regulation, which have been considered as the hallmark indicators of HDAC inhibition. AR-42 has been found to modulate several apoptosis inhibitors as well as cell survival regulator, including Akt, Bcl-xL, Bax, Ku70 and surviving, and exert potent antitumor activity against multiple tumor types, such as human prostate and hepatic cancers, at least partially through PI3K/Akt pathway inhibition.
Reference
[1].Matthew L. Bush†, Janet Oblinger†, Victoria Brendel, Griffin Santarelli, Jie Huang, Elena M. Akhmametyeva, Sarah S. Burns, Justin Wheeler, Jeremy Davis, Charles W. Yates, Abhik R. Chaudhury, Samuel Kulp, Ching-Shih Chen, Long-Sheng Chang, D. Bradley Welling, and Abraham Jacob. AR42, a novel histone deacetylase inhibitor, as a potential therapy for vestibular schwannomas and meningiomas. Neuro-Oncology 13(9):983–999, 2011
[2].Aaron M. Sargeant, Robert C. Rengel, Samuel K. Kulp, et al. OSU-HDAC42, a Histone Deacetylase Inhibitor, Blocks Prostate Tumor Progression in the Transgenic Adenocarcinoma of the Mouse Prostate Model Cancer Res 2008;68:3999-4009.
[3].Qiang Lu, Da-Sheng Wang, Chang-Shi Chen, Yuan-Dong Hu, and Ching-Shih Chen. Structure-Based Optimization of Phenylbutyrate-Derived Histone Deacetylase
[4].Inhibitors. J. Med. Chem. 2005, 48, 5530-5535
| Kinase experiment [1]: | |
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In vitro HDAC assay |
HDAC activity was analyzed by using an HDAC assay kit. This assay was based on the ability of DU-145 nuclear extract, which is rich in HDAC activity, to mediate the deacetylation of the biotinylated [3H]-acetyl histone H4 peptide that was bound to streptavidin agarose beads. The release of [3H]-acetate into the supernatant was measured to calculate the HDAC activity. Sodium butyrate (0.25 ~ 1 mM) was used as a positive control. |
| Cell experiment [1]: | |
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Cell lines |
DU-145 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months. |
|
Reaction Conditions |
10 ~ 1000 nM; 96 hrs |
|
Applications |
AR-42 inhibited the growth of DU-145 cells with an IC50 value of 0.11 μM. |
| Animal experiment [2]: | |
|
Animal models |
Intact male NCr athymic nude mice inoculated s.c. with PC-3 cells |
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Dosage form |
25 mg/kg, q.d., or 50 mg/kg, q.o.d.; p.o.; for 28 days |
|
Applications |
At the doses of 25 mg and 50 mg, AR-42 inhibited the growth of PC-3 tumor xenografts by 52% and 67%, respectively. |
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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]. Lu Q, Wang DS, Chen CS, Hu YD, Chen CS. Structure-based optimization of phenylbutyrate-derived histone deacetylase inhibitors. J Med Chem. 2005 Aug 25;48(17):5530-5. [2]. Kulp SK, Chen CS, Wang DS, Chen CY, Chen CS. Antitumor effects of a novel phenylbutyrate-based histone deacetylase inhibitor, (S)-HDAC-42, in prostate cancer. Clin Cancer Res. 2006 Sep 1;12(17):5199-206. | |
| Cas No. | 935881-37-1 | SDF | |
| Chemical Name | N-hydroxy-4-[[(2S)-3-methyl-2-phenylbutanoyl]amino]benzamide | ||
| Canonical SMILES | CC(C)C(C1=CC=CC=C1)C(=O)NC2=CC=C(C=C2)C(=O)NO | ||
| Formula | C18H20N2O3 | M.Wt | 312.36 |
| Solubility | ≥ 15.62 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 | 3.2014 mL | 16.0072 mL | 32.0143 mL |
| 5 mM | 0.6403 mL | 3.2014 mL | 6.4029 mL |
| 10 mM | 0.3201 mL | 1.6007 mL | 3.2014 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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