Home Epigenetics HDAC inhibitor AR-42 For research use only.

AR-42

Synonyms: HDAC-42

AR-42 (HDAC-42) is an HDAC inhibitor with IC50 of 30 nM. Phase 1.

AR-42 Chemical Structure

AR-42 Chemical Structure

CAS: 935881-37-1

Selleck's AR-42 has been cited by 25 Publications

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Purity & Quality Control

Batch: Purity: 99.03%
99.03

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Biological Activity

Description AR-42 (HDAC-42) is an HDAC inhibitor with IC50 of 30 nM. Phase 1.
Features Greater potency relative to SAHA.
Targets
HDAC [1]
(Cell-free assay)
30 nM
In vitro
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]
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.
Cell Research Cell lines DU-145
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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot gp130 / p-STAT3 / STAT3 / p-AKT / AKT / p-MEK / MEK Cyclin D1 / p21 / p16 / Cyclin A / Cyclin B1 Act-H3 / Act-H3 / Act-tubulin p-Kit / Kit Notch1 / NICD / Nestin / Zeb-1 / BMI-1 20824695
Growth inhibition assay Cell viability 26993777
In Vivo
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]
Animal Research Animal Models Intact male NCr athymic nude mice inoculated s.c. with PC-3 cells
Dosages ~50 mg/kg/day
Administration Orally
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02795819 Terminated Renal Cell Carcinoma|Soft Tissue Sarcoma|Metastatic Disease Virginia Commonwealth University|National Cancer Institute (NCI) July 8 2016 Phase 1
NCT02282917 Terminated Vestibular Schwannoma|Meningioma|Acoustic Neuroma|Neurofibromatosis Type 2 Massachusetts Eye and Ear Infirmary|Johns Hopkins University|Mayo Clinic|Stanford University|Ohio State University|Nationwide Children''s Hospital December 2015 Early Phase 1

Chemical lnformation & Solubility

Molecular Weight 312.36 Formula

C18H20N2O3
CAS No. 935881-37-1 SDF Download AR-42 SDF
Smiles CC(C)C(C1=CC=CC=C1)C(=O)NC2=CC=C(C=C2)C(=O)NO
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 63 mg/mL ( (201.69 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 63 mg/mL

Water : Insoluble


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In vivo
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