Antibodies
AR-42
- 貨號 Cat. No.
- S2244
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
AR-42
Catalog No.S2244
AR-42 is an HDAC inhibitor with IC50 of 30 nM.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | AR-42 is an HDAC inhibitor with IC50 of 30 nM. | |||||
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| Targets | HDAC | |||||
| IC50 | 30 nM [1] | |||||
| In vitro | AR-42 treatment induces histone hyperacetylation and p21WAF/CIP1 overexpression, and inhibits the growth of DU-145 cells with IC50 of 0.11 μM. [1] HDAC42 is potent in suppressing the proliferation of U87MG and PC-3 cells, in part, because of its ability to down-regulate Akt signaling. [2] AR-42 inhibits the growth of PC-3 and LNCaP cells with IC50 of 0.48 μM and 0.3 μM, respectively. Compared to SAHA, AR-42 exhibits distinctly superior apoptogenic potency, and causes markedly greater decreases in phospho-Akt, Bcl-xL, and survivin in PC-3 cells. [3] AR-42 treatment induces growth inhibition, cell- cycle arrest, apoptosis, and activation of caspases-3/7 in malignant mast cell lines. AR-42 treatment induces down-regulation of Kit via inhibition of Kit transcription, disassociation between Kit and heat shock protein 90 (HSP90), and up-regulation of HSP70. AR-42 treatment down-regulates the expression of p-Akt, total Akt, phosphorylated STAT3/5 (pSTAT3/5), and total STAT3/5. [6] AR-42 potently inhibits the growth of JeKo-1, Raji, and 697 cells with IC50 of <0.61 μM. AR-42 also sensitizes CLL cells to TNF-Related Apoptosis Inducing Ligand (TRAIL), potentially through reduction of c-FLIP.[7] AR-42 treatment also induces autophagy through downregulation of Akt/mTOR signaling and inducing ER stress in hepatocellular carcinoma (HCC) cells. [8] | |||||
| In vivo | The growth of PC-3 tumor xenografts is suppressed by 52% and 67% after treatment with AR-42 at 25 mg/kg and 50 mg/kg, respectively, whereas SAHA at 50 mg/kg suppresses growth by 31%. In contrast to mice treated with SAHA, intratumoral levels of phospho-Akt and Bcl-xL are markedly reduced in AR-42 treated mice. [3] In the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, administration of AR-42 not only decreases the severity of prostatic intraepithelial neoplasia (PIN) and completely prevents its progression to poorly differentiated carcinoma, but also shifts tumorigenesis to a more differentiated phenotype, suppressing absolute and relative urogenital tract weights by 86% and 85%, respectively. [5] AR-42 significantly reduces leukocyte counts, and prolongs survival in three separate mouse models of B-cell malignancy without evidence of toxicity. [7] | |||||
| Features | Greater potency relative to SAHA. | |||||
Protocol(Only for Reference)
Kinase Assay:
| In vitro HDAC assay | HDAC activity is analyzed by using an HDAC assay kit. This assay is 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 is bound to streptavidin agarose beads. The release of [3H]-acetate into the supernatant is measured to calculate the HDAC activity. Sodium butyrate (0.25-1 mM) is used as a positive control. |
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Cell Assay:
| Cell lines | DU-145 |
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| Concentrations | Dissolved in DMSO, final concentrations ~2.5 μM |
| Incubation Time | 96 hours |
| Method | Cells are exposed to varous concentrations of AR-42 for 96 hours. The medium is removed and replaced by 150 μL of 0.5 mg/mL of MTT in RPMI 1640 medium, and the cells are incubated in the CO2 incubator at 37 °C for 2 hours. Supernatants are removed from the wells, and the reduced MTT dye is solubilized with 200 μL/well of DMSO. Absorbance is determined on a plate reader at 570 nm. |
Animal Study:
| Animal Models | Intact male NCr athymic nude mice inoculated s.c. with PC-3 cells |
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| Dosages | ~50 mg/kg/day |
| Administration | Orally |
| Solubility | 0.5% methylcellulose/0.2% Tween 80, 30 mg/mL |
References
Chemical Information
| Molecular Weight (MW) | 312.36 |
|---|---|
| Formula | C18H20N2O3 |
| CAS No. | 935881-37-1 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | OSU-HDAC42 |
| Solubility (25°C) * | In vitro | DMSO | 63 mg/mL (201 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | 63 mg/mL (201 mM) | ||
| In vivo | 0.5% methylcellulose/0.2% Tween 80, | 30 mg/mL | |
| * <1 mg/ml means slightly soluble or insoluble. * 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 Name | (S)-N-hydroxy-4-(3-methyl-2-phenylbutanamido)benzamide |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
|---|---|---|---|---|
| Mass(mg) | 0.31236 | 3.1236 | 6.2472 | 9.3708 |
