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AR-42 (OSU-HDAC42)HDAC inhibitor,novel and potent

AR-42 (OSU-HDAC42)

Catalog No. A4104
Size Price Stock Qty
10mM (in 1mL DMSO) $130.00 In stock
Evaluation Sample $28.00 In stock
2mg $50.00 In stock
5mg $105.00 In stock
10mg $190.00 In stock
50mg $590.00 In stock

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Sample solution is provided at 25 µL, 10mM.

Product Citations

1.Park, Jeenah, Scott Thomas, and Pamela N. Munster. "Epigenetic modulation with histone deacetylase inhibitors in combination with immunotherapy." Epigenomics 7.4 (2015): 641-652. PMID:26111034

Quality Control

Chemical structure

AR-42 (OSU-HDAC42)

Related Biological Data

AR-42 (OSU-HDAC42)

Related Biological Data

AR-42 (OSU-HDAC42)

Biological Activity

Description AR-42 is an inhibitor of HDAC with IC50 of 30 nM.
Targets HDAC          
IC50 30 nM          

Protocol

Kinase experiment [1]:

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]:

Cell lines

DU-145 cells

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.

Reacting condition

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

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.

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.

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.

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Chemical Properties

Cas No. 935881-37-1 SDF Download 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 Soluble in DMSO > 10 mM Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

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Research Update

1. Histone deacetylase inhibitor AR-42 enhances E7-specific CD8⁺ T cell-mediated antitumor immunity induced by therapeutic HPV DNA vaccination. J Mol Med (Berl). 2013 Oct;91(10):1221-31. doi: 10.1007/s00109-013-1054-9. Epub 2013 May 29.
Abstract
The treatment of AR-42 and CRT/E7 DNA vaccine resulted in longer survival, decreased tumor growth and enhanced E7-specific immune response in HPV-16 E7-expressing murine TC-1 tumor-bearing mice compared to AR-42 or CRT/E7 DNA vaccine alone, which indicates AR-42 is capable of enhancing the potency of the CRT/E7 DNA vaccine by improving tumor-specific immune responses and antitumor effects. Moreover, AR-42 increased the surface expression of MHC class I molecules in TC-1 cells and its susceptibility to the cytotoxicity of E7-specific T cells.
2. Increased anti-leukemic activity of decitabine via AR-42-induced upregulation of miR-29b: a novel epigenetic-targeting approach in acute myeloid leukemia. Leukemia. 2013 Apr;27(4):871-8. doi: 10.1038/leu.2012.342. Epub 2012 Nov 26.
Abstract
AR-42 is a potent HDACI in AML that increases miR-29b levels and induces down-regulation of known miR-29n targets. The AR-42-and-then-decitabine regime exhibited stronger anti-leukemic activity in vitro and in vivo than the decitabine-and-then AR-42 regime and each mono-therapy.
3. Histone deacetylase inhibitor AR-42 differentially affects cell-cycle transit in meningeal and meningioma cells, potently inhibiting NF2-deficient meningioma growth. Cancer Res. 2013 Jan 15;73(2):792-803. doi: 10.1158/0008-5472.CAN-12-1888. Epub 2012 Nov 14.
Abstract
Although it inhibited cell proliferation in both Ben-Men-1 and meningeal cells through increasing the expression of p16(INK4A), P21(CIP1/WAF1) and p27(KIP1), AR-42 induced cell arrest at G(2)-M and significantly reduced cyclin B expression in Ben-Men-1 cells whereas induced cell arrest at G(1) and reduced expression of proliferating cell nuclear antigen and cyclins D1, E and A in meningeal cells. Additionally, AR-42 decreased the expression of Aurora A, Aurora B and Bcl(XL),increased Bim expression and caused regression of Ben-Men-1-LucB tumors.
4. The novel histone deacetylase inhibitor, AR-42, inhibits gp130/Stat3 pathway and induces apoptosis and cell cycle arrest in multiple myeloma cells. Int J Cancer. 2011 Jul 1;129(1):204-13. doi: 10.1002/ijc.25660. Epub 2010 Dec 1.
Abstract
AR-42 exhibited cytotoxicity against MM cells at a mean LC(50) of 0.18 ± 0.06 μmol/l, which induced apoptosis with cleavage of caspases 8,9 and 3 and affected gp130/STAT-3 pathway through down-regulation of expression of gp130 and STAT3-regulated targets and inhibition of STAT3 activation.

Background

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

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

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.

Qiang Lu, Da-Sheng Wang, Chang-Shi Chen, Yuan-Dong Hu, and Ching-Shih Chen. Structure-Based Optimization of Phenylbutyrate-Derived Histone Deacetylase

Inhibitors. J. Med. Chem. 2005, 48, 5530-5535