| Name | Resminostat |
| Description | Resminostat (4SC-201) is an orally bioavailable inhibitor of histone deacetylases (HDACs) with potential antineoplastic activity. |
| Cell Research | Cell lines: OPM-2,NCI-H929,RPMI-8226 and U266. Concentrations: ~ 10 μM. Method: WST-1 assay |
| Kinase Assay | Enzymatic HDAC activity assays: 40 μL 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 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, 10 μM for HDAC6 and 25 μM for HDAC3/DAD) or Ac-RHK(Ac)K(Ac)-AMC (HDAC8 assay, final concentration 50 μM). After incubation for 3 hours (HDAC1, HDAC6, HDAC8) or 2 hours (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 IC50, 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) is set at 0% enzymatic activity (background fluorescence substracted). |
| In vitro | Resminostat顯示出良好的PK曲線,具有高生物利用度和低pT變異性.口服Resminostat的表觀t 1/2范圍為2.7至4.4小時(shí).一天一次口服600 mg Resminostat,在14天的周期內(nèi)持續(xù)1-5天耐受性良好. |
| In vivo | Resminostat可激活Caspases 3,8 和9。Resminostat與Melphalan 和Proteasome inhibitors bortezomib 及S-2209有協(xié)同作用。Resminostat[HCl]可以誘導(dǎo)MM細(xì)胞組蛋白H4的高度乙?；?。 Resminostat可以阻止MM細(xì)胞系（OPM-2,NCI-H929,U266）中細(xì)胞生長和強(qiáng)力誘導(dǎo)細(xì)胞凋亡,同作用于初級(jí)MM細(xì)胞作用一致。1 μM Resminostat抑制MM細(xì)胞系（OPM-2,NCI-H929,U266）細(xì)胞增殖和誘導(dǎo)細(xì)胞周期的G0/G1期阻滯,同時(shí)伴隨著cyclin D1,CDC25A,CDK4和Rb的水平降低以及p21基因的上調(diào)。Resminostat通過降低4E-BP1和p70S6K的磷酸化來干擾Akt信號(hào)通路。Resminostat使Bim和Bax蛋白表達(dá)水平升高,Bcl-xL的水平降低。 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility Information | DMSO : 65 mg/mL (186 mM)
Ethanol : 65 mg/mL (186 mM)
H2O : <1 mg/mL
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| Keywords | Histone deacetylases | RAS 2410 | Inhibitor | HDAC | inhibit | RAS-2410 | 4SC201 | Resminostat | 4SC 201 |
| Inhibitors Related | Valproic acid sodium salt | 4-Phenylbutyric acid | Valproic Acid | Panobinostat | Theophylline | Acefylline | Curcumin | Theophylline monohydrate | Sodium 4-phenylbutyrate | Vorinostat |