AR-42

Catalog No.S2244 Synonyms: HDAC-42

For research use only.

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

AR-42 Chemical Structure

CAS No. 935881-37-1

Selleck's AR-42 has been cited by 24 publications

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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

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]

Assay
Methods Test Index 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 20233974 26625202
Growth inhibition assay Cell viability 26993777
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]

Protocol (from reference)

Kinase Assay:

[1]

  • 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:

[1]

  • 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.

Animal Research:

[3]

  • Animal Models: Intact male NCr athymic nude mice inoculated s.c. with PC-3 cells
  • Dosages: ~50 mg/kg/day
  • Administration: Orally

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
0.5% methylcellulose+0.2% Tween 80
For best results, use promptly after mixing.

30 mg/mL

Chemical Information

Molecular Weight 312.36
Formula

C18H20N2O3

CAS No. 935881-37-1
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC(C)C(C1=CC=CC=C1)C(=O)NC2=CC=C(C=C2)C(=O)NO

In vivo Formulation Calculator (Clear solution)

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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.

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Molarity Calculator

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02795819 Terminated Drug: AR-42|Drug: Pazopanib Renal Cell Carcinoma|Soft Tissue Sarcoma|Metastatic Disease Virginia Commonwealth University|National Cancer Institute (NCI) July 8 2016 Phase 1
NCT02282917 Terminated Drug: AR-42 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

(data from https://clinicaltrials.gov, updated on 2022-08-01)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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