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Resminostat (formerly RAS-2410; 4SC-201) is a potent inhibitor of classes I and II HDACs (histone deacetylases) such as HDAC1/3/6 with potential anticancer activity. With IC50 values between 43 and 72 nmol/L, it inhibits HDAC1/3/6. Both in vivo and in vitro antitumor efficaciousness are strong points of this substance. 4SC is exploring the use of resminostat as a liver cancer treatment partner with Yakult in Japan.
Physicochemical Properties
| Molecular Formula | C16H19N3O4S |
| Molecular Weight | 349.4 |
| Exact Mass | 349.109 |
| Elemental Analysis | C, 55.00; H, 5.48; N, 12.03; O, 18.32; S, 9.18 |
| CAS # | 864814-88-0 |
| Related CAS # | 1187075-34-8 (HCl); 864814-88-0(free base) |
| PubChem CID | 11609955 |
| Appearance | Solid powder |
| Density | 1.3±0.1 g/cm3 |
| Index of Refraction | 1.600 |
| LogP | 1.69 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 24 |
| Complexity | 548 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | S(C1C=CC(CN(C)C)=CC=1)(N1C=CC(/C=C/C(=O)NO)=C1)(=O)=O |
| InChi Key | FECGNJPYVFEKOD-VMPITWQZSA-N |
| InChi Code | InChI=1S/C16H19N3O4S/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)/b8-5+ |
| Chemical Name | (E)-3-[1-[4-[(dimethylamino)methyl]phenyl]sulfonylpyrrol-3-yl]-N-hydroxyprop-2-enamide |
| Synonyms | RAS2410; RAS-2410; RAS2410; RAS 2410; 4SC201; 4SC-201; 4SC 201; Resminostat |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | HDAC1 ( IC50 = 42.5 nM ); HDAC3 ( IC50 = 50.1 nM ); HDAC6 ( IC50 = 71.8 nM ); HDAC8 ( IC50 = 877 nM ) | ||
| ln Vitro |
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| ln Vivo |
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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]. | ||
| Cell Assay | The antiproliferative effect of resminostat on HNSCC cells is examined using a CCK-8 cell proliferation assay. Three × 105 cells per well are seeded into 96-well plates. Following a 24-hour growth period, the cells undergo treatment with resminostat and cisplatin, either separately or in conjunction, and are then incubated for a full 72 hours. Equal amounts of dimethylsulfoxide were used as a control group along with untreated cells that were kept in RPMI. CCK-8 is used to measure the proliferation of cells after 72 hours. Three times, each experiment is conducted in triplicate[2]. | ||
| Animal Protocol |
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| References |
[1]. The novel inhibitor of histone deacetylase resminostat (RAS2410) inhibits proliferation and induces apoptosis in multiple myeloma (MM) cells. Br J Haematol. 2010 May;149(4):518-28. [2]. Effect of the histone deacetylase inhibitor resminostat on head and neck squamous cell carcinoma cell lines. Head Neck. 2017 May;39(5):900-907. [3]. mTOR inhibition sensitizes human hepatocellular carcinoma cells to resminostat. Biochem Biophys Res Commun. 2016 Sep 2;477(4):556-562. |
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| Additional Infomation |
Resminostat is an enamide resulting from the formal condensation of the carboxy group of (2E)-3-[1-({4-[(dimethylamino)methyl]phenyl}sulfonyl)-1H-pyrrol-3-yl]prop-2-enoic acid with the amino group of hydroxylamine. It is an orally bioavailable inhibitor of histone deacetylases with potential antineoplastic activity. It has a role as an EC 3.5.1.98 (histone deacetylase) inhibitor, an antineoplastic agent and an apoptosis inducer. It is a member of benzenes, a sulfonamide, a member of pyrroles, a tertiary amino compound, a hydroxamic acid and an enamide. Resminostat has been used in trials studying the treatment of Sezary Syndrome, Mycosis fungoides, Hodgkin's Lymphoma, Hepatocellular Carcinoma, and Lymphoma, T-Cell, Cutaneous, among others. Resminostat is an orally bioavailable inhibitor of histone deacetylases (HDACs) with potential antineoplastic activity. Resminostat binds to and inhibits HDACs leading to an accumulation of highly acetylated histones. This may result in an induction of chromatin remodeling, inhibition of the transcription of tumor suppressor genes, inhibition of tumor cell division and the induction of tumor cell apoptosis. HDACs, upregulated in many tumor types, are a class of enzymes that deacetylate chromatin histone proteins. Drug Indication Treatment of Cutaneous T-Cell Lymphoma |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8620 mL | 14.3102 mL | 28.6205 mL | |
| 5 mM | 0.5724 mL | 2.8620 mL | 5.7241 mL | |
| 10 mM | 0.2862 mL | 1.4310 mL | 2.8620 mL |