Resminostat

Catalog No.S2693 Synonyms: RAS2410

For research use only.

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.

Resminostat Chemical Structure

CAS No. 864814-88-0

Selleck's Resminostat has been cited by 7 Publications

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Biological Activity

Description 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.
Targets
HDAC1 [1] HDAC3 [1] HDAC6 [1]
42.5 nM 50.1 nM 71.8 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]

Protocol (from reference)

Kinase Assay:[1]
  • 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).

Cell Research:[1]
  • Cell lines: OPM-2, NCI-H929, RPMI-8226 and U266
  • Concentrations: ~ 10 μM
  • Incubation Time: 48, 96 h
  • Method: WST-1 assay

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 349.4
Formula

C16H19N3O4S

CAS No. 864814-88-0
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CN(C)CC1=CC=C(C=C1)S(=O)(=O)N2C=CC(=C2)C=CC(=O)NO

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04955340 Completed Drug: [14C]-resminostat Cutaneous T Cell Lymphoma|Mycosis Fungoides|Sezary Syndrome 4SC AG October 12 2021 Phase 1
NCT01277406 Completed Drug: 4SC-201(Resminostat)|Drug: FOLFIRI Advanced Colorectal Carcinoma 4SC AG January 2011 Phase 1|Phase 2
NCT01037478 Completed Drug: Resminostat (4SC-201) Hodgkin''s Lymphoma 4SC AG December 2009 Phase 2

(data from https://clinicaltrials.gov, updated on 2022-08-01)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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