Name: AR-42
Brand: Selleck Chemicals
SKU: S2244
Availability: InStock
Rating: 5 (30 reviews)

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Quality Control

Batch: Purity: 99.03%

99.03

Related Targets	JAK BET Histone Methyltransferase PKC PARP HIF PRMT EZH2 AMPK Histone Acetyltransferase
Other HDAC Inhibitors	ITF-2357 (Givinostat) Hydrochloride Monohydrate Fimepinostat (CUDC-907) Trichostatin A (TSA) Entinostat (MS-275) RGFP966 Quisinostat (JNJ-26481585) Dihydrochloride Tubastatin A Hydrochloride Tubastatin A Mocetinostat (MGCD0103) Ricolinostat (ACY-1215)

Solubility

In vitro
Batch:

DMSO : 63 mg/mL (201.69 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 63 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	0.5% methylcellulose 1 0.2% Tween 80 Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	10.000mg/ml (32.01mM)	Taking the 1 mL working solution as an example, take 10 mg of this product, add it to 1 ml of 0.5% methylcellulose+0.2% Tween 80 clear solution, and mix evenly to make it a uniform suspension. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

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Average weight of animals: g

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% DMSO

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% Tween 80

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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.

Chemical Information, Storage & Stability

Molecular Weight	312.36	Formula	C₁₈H₂₀N₂O₃	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	935881-37-1	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	HDAC-42			SMILES	CC(C)C(C1=CC=CC=C1)C(=O)NC2=CC=C(C=C2)C(=O)NO

Read more about storage stability stock solution CAS number SMILES

Mechanism of Action

Features	Greater potency relative to SAHA.
Targets/IC₅₀/Ki	HDAC (Cell-free assay) 30 nM
In vitro	AR-42 treatment induces histone hyperacetylation and p21^WAF/CIP1 overexpression, and inhibits the growth of DU-145 cells with IC50 of 0.11 μM. This compound is potent in suppressing the proliferation of U87MG and PC-3 cells, in part, because of its ability to down-regulate Akt signaling. It inhibits the growth of PC-3 and LNCaP cells with IC50 of 0.48 μM and 0.3 μM, respectively. Compared to SAHA, this chemical exhibits distinctly superior apoptogenic potency, and causes markedly greater decreases in phospho-Akt, Bcl-xL, and survivin in PC-3 cells. This compound treatment induces growth inhibition, cell- cycle arrest, apoptosis, and activation of caspases-3/7 in malignant mast cell lines. It induces down-regulation of Kit via inhibition of Kit transcription, disassociation between Kit and heat shock protein 90 (HSP90), and up-regulation of HSP70. This treatment down-regulates the expression of p-Akt, total Akt, phosphorylated STAT3/5 (pSTAT3/5), and total STAT3/5. It potently inhibits the growth of JeKo-1, Raji, and 697 cells with IC50 of <0.61 μM. This compound also sensitizes CLL cells to TNF-Related Apoptosis Inducing Ligand (TRAIL), potentially through reduction of c-FLIP. This treatment also induces autophagy through downregulation of Akt/mTOR signaling and inducing ER stress in hepatocellular carcinoma (HCC) cells.
Kinase Assay	In vitro HDAC assay
Kinase 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.
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 this compound treated mice. In the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, administration of this chemical 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. This agent significantly reduces leukocyte counts, and prolongs survival in three separate mouse models of B-cell malignancy without evidence of toxicity.
References	[1] https://pubmed.ncbi.nlm.nih.gov/16107152/ [2] https://pubmed.ncbi.nlm.nih.gov/16186112/ [3] https://pubmed.ncbi.nlm.nih.gov/16951239/ [4] https://pubmed.ncbi.nlm.nih.gov/17545612/ [5] https://pubmed.ncbi.nlm.nih.gov/18483287/ [6] https://pubmed.ncbi.nlm.nih.gov/20233974/ [7] https://pubmed.ncbi.nlm.nih.gov/20532179/ [8] https://pubmed.ncbi.nlm.nih.gov/20962572/

Applications

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

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2021-06-15)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT02569320	COMPLETED	Recurrent Plasma Cell Myeloma	Ohio State University Comprehensive Cancer Center	2016-05-20	PHASE1
NCT02282917	TERMINATED	Vestibular Schwannoma; Meningioma; Acoustic Neuroma; Neurofibromatosis Type 2	Massachusetts Eye and Ear Infirmary	2015-12	EARLY_PHASE1
NCT01129193	COMPLETED	Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia	Amir Mortazavi	2010-05-04	PHASE1
NCT02795819	TERMINATED	Renal Cell Carcinoma; Soft Tissue Sarcoma; Metastatic Disease	Virginia Commonwealth University	2016-07-08	PHASE1
NCT02795819	Terminated	Renal Cell Carcinoma\|Soft Tissue Sarcoma\|Metastatic Disease	Virginia Commonwealth University\|National Cancer Institute (NCI)	2016-07-08	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	2015-12	Early Phase 1

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AR-42 HDAC inhibitor

Chemical Structure

Molecular Weight: 312.36