Pracinostat (SB939)

製品コードS1515 バッチS151505

印刷

化学情報

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

C20H30N4O2
分子量 358.48 CAS No. 929016-96-6
Solubility (25°C)* 体外 DMSO 72 mg/mL (200.84 mM)
Ethanol 32 mg/mL (89.26 mM)
Water Insoluble
* <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 Pracinostat (SB939) is a potent pan-HDAC inhibitor with IC50 of 40-140 nM with exception for HDAC6. It has no activity against the class III isoenzyme SIRT I. Pracinostat (SB939) induces apoptosis in tumor cells. Phase 2.
in vitro SB939 has a 100-fold greater selectivity for HDACs than for Zn-binding non-HDAC enzymes, receptors, and ion channels. SB939 is a potent inhibitor of HDAC class I isoenzymes, HDAC1, HDAC2, HDAC3 and HDAC8 with the IC50 values ranging from 43 nM to 140 nM. SB939 inhibits HDAC class II isoenzymes , HDAC4, HDAC5, HDAC7, HDAC9 and HDAC10 significantly with the IC50 values ranging from 40 nM to 137 nM, with the exception of HDAC6 which shows IC50 of 1008 nM. It markedly inhibits HDAC11 of the HDAC class IV enzymes with IC50 of 93 nM, but shows no inhibitory activity against SIRT 1 of the class III HDACs. SB939 shows significant antiproliferative activity against a wide variety of tumor cell lines, especially Leukemia cells and cutaneous T-cell Lymphoma cells with IC50 values ranging from 50 nM (H9 cells) to 170 nM (HEL92.1.7 cells). [1]
in vivo Administration of SB939 (25 mg/kg to 100 mg/kg) displays a dose-dependent antitumor efficacy in a xenograft mice model of human colorectal cancer (HCT-116). This is approximately twice as efficacious as SAHA: SB939 causing a tumor growth inhibition of 94% versus 48% by SAHA with both at the maximum tolerated dose. Oral administration of SB939 at a dose of 50 mg/kg or 75 mg/kg in the APCmin genetic mice model of early-stage colon cancer markedly reduces the number of tumors , decreases cumulative hemocult scores and increases hematocrit values more effectively than 5-fluorouracil. [1]
特徴 A new histone deacetylase inhibitor based on hydroxamic acid, with improved physicochemical, pharmaceutical, and pharmacokinetic properties.

プロトコル(参考用のみ)

キナーゼアッセイ HDAC enzyme assay
All recombinant HDAC enzymes, with the exception of SIRT1, are cloned and expressed in S*BIO. The reaction mix containing 2.5 or 5 μL of the HDAC isoenzyme, assay buffer (25 mM Tris-HCl, pH 7.5; 137 mM NaCl; 2.7 mM KCl, 1 mM MgCl2 and 1 mg/mL BSA), different concentrations of SB939, and the fluorogenic deacetylase substrate Flour de LysTM in a total reaction volume of 33 μL is incubated at room temperature for 2 hours. 16 μL of Flour de LysTM developer is added and incubated for an additional 10 minutes. The emitted light is measured at 460 nm in a microplate reader. IC50 values are generated using the XLfit software.
細胞アッセイ 細胞株 HCT116, A2780, ACHN, MCF7, HL-60, et al.
濃度 Dissolved in DMSO (stock concentration, 10 mM), final concentrations 1.5 nM to 100 μM
反応時間 96 hours
実験の流れ Cells are seeded in 96-well plates in the log growth phase at a predetermined optimal density, and rested for 24 hours (adherent cells) or 2 hours (suspension cells), respectively. They are exposed to different concentrations of SB939 for 96 hours. Cell proliferation assays are done using either the CyQUANT cell proliferation assay kit for adherent cells or the CellTiter96 Aqueous One solution cell proliferation kit for suspension cells.
動物実験 動物モデル BALB/c nude mice bearing HCT-116 human colon cancer xenografts, Male and APCmin mice
投薬量 25, 50, 75, or 100 mg/kg
投与方法 Oral gavage once daily

カスタマーフィードバック

Data from [Data independently produced by Antimicrob Agents Chemother, 2012, 56(7), 3849-56]

Data independently produced by , , Dr. Zhang of Tianjin Medical University

Data from [Data independently produced by , , Oncotarget, 2016, 7(23):34384-94]

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：

Epigenetic and molecular coordination between HDAC2 and SMAD3-SKI regulates essential brain tumour stem cell characteristics [ Nat Commun, 2023, 14(1):5051] PubMed: 37598220
Epigenetic and molecular coordination between HDAC2 and SMAD3-SKI regulates essential brain tumour stem cell characteristics [ Nat Commun, 2023, 14(1):5051] PubMed: 37598220
Nuclear oligo hashing improves differential analysis of single-cell RNA-seq [ Nat Commun, 2022, 13(1):2666] PubMed: 35562344
The novel histone deacetylase inhibitor pracinostat suppresses the malignant phenotype in human glioma [ Mol Biol Rep, 2022, 10.1007/s11033-022-07559-y] PubMed: 35622308
CREBBP cooperates with the cell cycle machinery to attenuate chidamide sensitivity in relapsed/refractory diffuse large B-cell lymphoma [ Cancer Lett, 2021, 521:268-280] PubMed: 34481935
Exposure of Microglia to Interleukin-4 Represses NF-κB-Dependent Transcription of Toll-Like Receptor-Induced Cytokines [ Front Immunol, 2021, 12:771453] PubMed: 34880868
Identification of Required Host Factors for SARS-CoV-2 Infection in Human Cells [ Cell, 2020, S0092-8674(20)31394-5] PubMed: 33147445
Pracinostat (SB939), a histone deacetylase inhibitor, suppresses breast cancer metastasis and growth by inactivating the IL-6/STAT3 signalling pathways. [ Life Sci, 2020, 248:117469] PubMed: 32109485
Targeting NAD+ Biosynthesis Overcomes Panobinostat and Bortezomib-Induced Malignant Glioma Resistance [ Mol Cancer Res, 2020, 18(7):1004-1017] PubMed: 32238439
Targeting NAD+ biosynthesis overcomes panobinostat and bortezomib-induced malignant glioma resistance. [ Mol Cancer Res, 2020, 10.1158/1541-7786.MCR-19-0669] PubMed: 32238439

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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