AR-42

製品コードS2244 バッチS224401

印刷

化学情報

Chemical Structure Synonyms HDAC-42 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C18H20N2O3
分子量 312.36 CAS No. 935881-37-1
Solubility (25°C)* 体外 DMSO 63 mg/mL (201.69 mM)
Ethanol 63 mg/mL (201.69 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
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.
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 AR-42 (HDAC-42) is an HDAC inhibitor with IC50 of 30 nM. Phase 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] 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. [2] 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. [3] 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. [6] 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. [7] This 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 this compound treated mice. [3] 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. [5] This agent significantly reduces leukocyte counts, and prolongs survival in three separate mouse models of B-cell malignancy without evidence of toxicity. [7]
特徴 Greater potency relative to SAHA.

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 細胞株 DU-145
濃度 Dissolved in DMSO, final concentrations ~2.5 μM
反応時間 96 hours
実験の流れ

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.
動物実験 動物モデル Intact male NCr athymic nude mice inoculated s.c. with PC-3 cells
投薬量 ~50 mg/kg/day
投与方法 Orally

参考

  • https://pubmed.ncbi.nlm.nih.gov/16107152/
  • https://pubmed.ncbi.nlm.nih.gov/16186112/
  • https://pubmed.ncbi.nlm.nih.gov/16951239/
  • https://pubmed.ncbi.nlm.nih.gov/17545612/
  • https://pubmed.ncbi.nlm.nih.gov/18483287/
  • https://pubmed.ncbi.nlm.nih.gov/20233974/
  • https://pubmed.ncbi.nlm.nih.gov/20532179/
  • https://pubmed.ncbi.nlm.nih.gov/20962572/

カスタマーフィードバック

Data from [Data independently produced by Sci Transl Med, 2014, 6(256), 256ra135]

Data from [Data independently produced by Leuk Res, 2014, 8(11), 1320-6]

, , J Cell Physiol, 2017, 233(1):559-571

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Orthogonal proteogenomic analysis identifies the druggable PA2G4-MYC axis in 3q26 AML [ Nat Commun, 2024, 15(1):4739] PubMed: 38834613
Targeting histone deacetylase 6 (HDAC6) to enhance radiation therapy in meningiomas in a 2D and 3D in vitro study [ EBioMedicine, 2024, 105:105211] PubMed: 38917510
Fermented Wheat Germ Protein with Histone Deacetylase Inhibitor AR42 Demonstrates Enhanced Cytotoxicity against Lymphoma Cells In Vitro and In Vivo [ Int J Mol Sci, 2024, 25(14)7866] PubMed: 39063110
Peripheral blood DNA methylation and neuroanatomical responses to HDACi treatment that rescues neurological deficits in a Kabuki syndrome mouse model [ Clin Epigenetics, 2023, 10.1186/s13148-023-01582-x] PubMed: 37884963
Peripheral blood DNA methylation and neuroanatomical responses to HDACi treatment that rescues neurological deficits in a Kabuki syndrome mouse model [ Clin Epigenetics, 2023, 15(1):172] PubMed: 37884963
Utilizing an Endogenous Progesterone Receptor Reporter Gene for Drug Screening and Mechanistic Study in Endometrial Cancer [ Cancers (Basel), 2022, 14(19)4883] PubMed: 36230806
The histone H3-lysine 4-methyltransferase Mll4 regulates the development of growth hormone-releasing hormone-producing neurons in the mouse hypothalamus [ Nat Commun, 2021, 12(1):256] PubMed: 33431871
KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer. [ Cancer Cell, 2020, 13;37(4):599-617 e7] PubMed: 32243837
A library of aminoglycoside-derived lipopolymer nanoparticles for delivery of small molecules and nucleic acids [ J Mater Chem B, 2020, 8(37):8558-8572] PubMed: 32830211
Identification of Combinations of Protein Kinase C Activators and Histone Deacetylase Inhibitors That Potently Reactivate Latent HIV [ Viruses, 2020, 3;12(6):E609] PubMed: 32503121

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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