Resminostat

製品コードS2693 バッチS269301

印刷

化学情報

Chemical Structure Synonyms RAS2410 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C16H19N3O4S
分子量 349.4 CAS No. 864814-88-0
Solubility (25°C)* 体外 DMSO 70 mg/mL (200.34 mM)
Ethanol 70 mg/mL (200.34 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 Resminostat (RAS2410) dose-dependently and selectively inhibits HDAC1/3/6 with IC50 of 42.5 nM/50.1 nM/71.8 nM, less potent to HDAC8 with IC50 of 877 nM.
in vitro Resminostat [HCl] is acting as a potent inhibitor of recombinant HDAC 1, 3 and 6 isoenzymes with a substrate competitive binding mode. It can induce hyperacetylation of histone H4 in MM cells. Low micromolar concentrations of resminostat abrogates cell growth and strongly induces apoptosis in MM cell lines (OPM-2, NCI-H929, U266 ) as well as primary MM cells. At 1 μM, resminostat inhibits proliferation and induces G0/G1 cell cycle arrest in OPM-2, NCI-H929, U266 MM cell lines accompanied with decreased levels of cyclin D1, cdc25a, Cdk4 and pRb as well as upregulation of p21. Resminostat decreases phosphorylation of 4E-BP1 and p70S6k indicating an interference with Akt pathway signalling. Treatment with resminostat results in increased protein levels of Bim and Bax and decreases levels of Bcl-xL. Caspases 3, 8 and 9 are activated by resminostat. Furthermore, synergistic effects are observed for combinations of resminostat with melphalan and the proteasome inhibitors bortezomib and S-2209. [1]
in vivo Oral resminostat at 600 mg QD continuously d1−5 in a 14 day cycle is well-tolerated. Resminostat shows a favourable PK profile, with high bioavailability and low inter-pt variability. The apparent t 1/2 of oral resminostat ranged from 2.7 to 4.4 hours. The modulation of plasma biomarkers further indicates drug activity. [2]

プロトコル(参考用のみ)

キナーゼアッセイ Enzymatic HDAC activity assays
Forty microliter enzyme buffer (15 mM Tris HCl pH 8.1, 0.25 mM EDTA, 250 mM NaCl, 10% v:v glycerol) containing HDAC1, 3, 6 or 8 activity, 29 μL enzyme buffer and 1 μL resminostat [HCl] at different concentrations are added to a 96-well microtitre plate and the reaction started by the addition of 30μL substrate peptide Ac-NH-GGK(Ac)-AMC (HDAC1, 3 and 6 assays, final concentrations 6 μM for HDAC1, 10μM for HDAC6 and 25μM for HDAC3/DAD) or Ac-RHK(Ac)K(Ac)-AMC (HDAC8 assay, final concentration 50 μM). After incubation for 180 min (HDAC1, HDAC6, HDAC8) or 120 min (HDAC3) at 30°C, the reaction is terminated by the addition of 25 μL stop solution (50 mM Tris HCl pH 8, 100 mM NaCl, 0.5 mg/ml trypsin and 2 μM trichostatin A [TSA]). After incubation at room temperature for further 40 min, fluorescence is measured using a multilabel counter (extinction 355 nm, emission 460 nm) for quantification of AMC generated by tryptic cleavage of the deacetylated peptide. For the calculation of the 50% inhibitory concentration (IC50) values the fluorescence in wells without test compound (1% DMSO, negative control) is set as 100% enzymatic activity and the fluorescence in wells with 2 μM TSA (positive control) are set at 0% enzymatic activity (background fluorescence substracted).
細胞アッセイ 細胞株 OPM-2, NCI-H929, RPMI-8226 and U266
濃度 ~ 10 μM
反応時間 48, 96 h
実験の流れ WST-1 assay

カスタマーフィードバック

Data from [Data independently produced by , , Head Neck, 2017, 39(5):900-907]

Data from [Data independently produced by , , Head Neck, 2017, 39(5):900-907.]

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：

HDAC Inhibitor, CG-745, Enhances the Anti-Cancer Effect of Anti-PD-1 Immune Checkpoint Inhibitor by Modulation of the Immune Microenvironment. [ J Cancer, 2020, 6;11(14):4059-4072] PubMed: 32368288
Selective Inhibition of HDAC6 Sensitizes Cutaneous T-cell Lymphoma to PI3K Inhibitors [ Oncol Lett, 2020, 20(1):533-540] PubMed: 32565979
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
Epigenetic Reprogramming with Antisense Oligonucleotides Enhances the Effectiveness of Androgen Receptor Inhibition in Castration-Resistant Prostate Cancer [ Cancer Res, 2018, 78(20):5731-5740] PubMed: 30135193
Upregulation of PD‑L1 expression by resveratrol and piceatannol in breast and colorectal cancer cells occurs via HDAC3/p300‑mediated NF‑κB signaling [Lucas J, et al. Int J Oncol, 2018, 53(4):1469-1480] PubMed: 30066852
Effect of the histone deacetylase inhibitor resminostat on head and neck squamous cell carcinoma cell lines [Enzenhofer E, et al. Head Neck, 2017, 39(5):900-907] PubMed: 28170128
Novel chemoimmunotherapeutic strategy for hepatocellular carcinoma based on a genome-wide association study. [ Sci Rep, 2016, 6:38407] PubMed: 27910927

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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