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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
Resminostat HCl (formerly known as RAS-2410; RAS2410 and 4SC-201), the hydrochloride salt of Resminostat, is a potent inhibitor of HDAC (histone deacetylase) classes I and II (including HDAC1/3/6) with anticancer activity. With IC50 values ranging from 43 to 72 nmol/L, it inhibits class I and II HDACs. Due to its capacity to cause apoptosis and histone H4 hyperacetylation in MM cells, resminostate has the potential to be used in the treatment of MM. According to recent study findings, resminostat inhibits the growth of MM cell lines, suppresses proliferation, induces G0/G1 cell cycle arrest, and interferes with the Akt signaling pathway by lowering the phosphorylation of p70S6k and 4E-BP1.
| Targets |
HDAC1 (IC50 = 0.31 nM); HDAC3 (IC50 = 0.83 nM); HDAC6 (IC50 = 71.8 nM); HDAC8 (IC50 = 877 nM)
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| ln Vitro |
Resminostat hydrochloride (Resminostat [HCl], 5 μM) causes histone acetylation in myeloma cells. With a mean Ki value of 27 nM, resminostat hydrochloride exhibits a substrate competitive binding mode. In myeloma cells, resminostat hydrochloride (5 μM) causes histone hyperacetylation. Resminostat suppresses MM cell proliferation, triggers apoptosis, and prevents cell growth. Additionally, resminostat (5 μM) inhibits signalling downstream of Akt and modifies the expression of proteins in the bcl-2 family. When combined with both established and novel anti-myeloma agents, resminostat exhibits synergistic activity against myeloma cells[1]. Resminostat shows IC50s ranging from 0.775 μM to 1.572 μM (IC50 for SCC25: 0.775 μM, CAL27: 1.572 μM, and FaDu: 0.899 μM) in head and neck squamous cell carcinoma cell lines, indicating that it inhibits cell growth. HNSCC cell lines respond well to both irradiation and resminostat (1.25 and 2.5 μM). One can downregulate survivin by combining resminostat with cisplatin. On Mcl-1 and p-AKT expression, however, Resminostat has no effect[2]. With IC50s ranging from 0.89 ± 0.12 μM to 0.07 ± 0.01 μM, respinostat decreases the viability of HCC cells when used in conjunction with AZD-2014[3].
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| ln Vivo |
Resminostat taken orally at 600 mg QD every day for 1–5 days in a 14-day cycle is well tolerated. With low inter-pt variability and high bioavailability, resminostat exhibits a favorable pharmacokinetic profile. Oral resminostat's apparent t 1/2 varied from 2.7 to 4.4 hours. Additional evidence of medication activity is the modulation of plasma biomarkers.
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| Enzyme Assay |
A 96-well microtitre plate is filled with 40 microliters of 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 microliters of enzyme buffer, and 1 microliter of resminostat [HCl] at varying concentrations. The reaction is initiated by adding 30 microliters of substrate peptide Ac-NH-GGK(Ac)-AMC (HDAC1, 3 and 6 assays, final concentrations of 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). The reaction is stopped by adding 25 μL of stop solution (50 mM Tris HCl pH 8, 100 mM NaCl, 0.5 mg/mL trypsin, and 2 μM trichostatin A [TSA]) after the enzymes have been incubated for 180 min (HDAC1, HDAC6, HDAC8) or 120 min (HDAC3) at 30°C. The quantification of AMC produced by tryptic cleavage of the deacetylated peptide is done using a Wallac Victor2 1420 multilabel counter (extinction 355 nm, emission 460 nm) following an additional 40 minutes of room temperature incubation. The fluorescence in wells without test compound (1% DMSO, negative control) is set to 100% enzymatic activity for the calculation of the 50% inhibitory concentration (IC50) values, while the fluorescence in wells with 2 μM TSA (positive control) is set to 0% enzymatic activity (background fluorescence substracted)[1].
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| Cell Assay |
The antiproliferative action of resminostat on HNSCC cells is examined using a CCK-8 cell proliferation assay. 3 × 105 cells per well are seeded into 96-well plates. The cells are treated with resminostat and cisplatin, either separately or together, after growing for 24 hours, and they are then incubated for 72 hours. As a control, untreated cells were kept in RPMI with equal amounts of dimethyl sulfoxide. CCK-8 is used to measure cell proliferation after 72 hours. Three times, each experiment is run in triplicate[2].
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| Animal Protocol |
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| References |
| Molecular Formula |
C16H20CLN3O4S
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| Molecular Weight |
385.86
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| Exact Mass |
385.086305
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| Elemental Analysis |
C, 49.80; H, 5.22; Cl, 9.19; N, 10.89; O, 16.59; S, 8.31
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| CAS # |
1187075-34-8
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| Related CAS # |
Resminostat;864814-88-0
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| Appearance |
Solid powder
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| SMILES |
CN(C)CC1=CC=C(C=C1)S(=O)(=O)N2C=CC(=C2)/C=C/C(=O)NO.Cl
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| InChi Key |
BVXPKDRKHXARHY-HAAWTFQLSA-N
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| InChi Code |
InChI=1S/C16H19N3O4S.ClH/c1-18(2)11-13-3-6-15(7-4-13)24(22,23)19-10-9-14(12-19)5-8-16(20)17-21;/h3-10,12,21H,11H2,1-2H3,(H,17,20);1H/b8-5+;
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| Chemical Name |
(E)-3-[1-[4-[(dimethylamino)methyl]phenyl]sulfonylpyrrol-3-yl]-N-hydroxyprop-2-enamide;hydrochloride
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (5.39 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.08 mg/mL (5.39 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.39 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5916 mL | 12.9581 mL | 25.9161 mL | |
| 5 mM | 0.5183 mL | 2.5916 mL | 5.1832 mL | |
| 10 mM | 0.2592 mL | 1.2958 mL | 2.5916 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Resminostat synergizes with common and new anti‐myeloma agents.Br J Haematol. 2010 May;149(4):518-28. |
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 Resminostat inhibits cell growth and induces apoptosis in MM cells.Br J Haematol. 2010 May;149(4):518-28. |
 Resminostat modulates expression of bcl-2 family proteins and inhibits Akt pathway signalling downstream of Akt.Br J Haematol.2010 May;149(4):518-28. |
 Resminostat induces histone acetylation in myeloma cells.Br J Haematol. 2010 May;149(4):518-28. |
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 Resminostat inhibits MM cell proliferation. Br J Haematol. 2010 May;149(4):518-28.Br J Haematol. 2010 May;149(4):518-28. |
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