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化学情報
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Synonyms | HDAC-42 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C18H20N2O3 |
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| 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 | |||
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* <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. |
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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. |
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| 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] |
| 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 | |
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| 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. |
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| 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
カスタマーフィードバック
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Data from [Data independently produced by Sci Transl Med, 2014, 6(256), 256ra135]
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Data from [Data independently produced by Leuk Res, 2014, 8(11), 1320-6]
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, , 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：
| 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 |
| Heme oxygenase-1 reduces the sensitivity to imatinib through nonselective activation of histone deacetylases in chronic myeloid leukemia [Wei D, et al. J Cell Physiol, 2019, 234(4):5252-5263] | PubMed: 30256411 |
| Functional analysis of RPS27 mutations and expression in melanoma. [ Pigment Cell Melanoma Res, 2019, 10.1111/pcmr.12841] | PubMed: 31663663 |
| Structural Basis of Catalysis and Inhibition of HDAC6 CD1, the Enigmatic Catalytic Domain of Histone Deacetylase 6 [ Biochemistry, 2019, 58(49):4912-4924] | PubMed: 31755702 |
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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