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Resminostat HDAC inhibitor

Cat.No.S2693

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 HDAC inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 349.4

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Quality Control

Batch: S269301 DMSO]70 mg/mL]false]Ethanol]70 mg/mL]false]Water]Insoluble]false Purity: 99.04%
99.04

Chemical Information, Storage & Stability

Molecular Weight 349.4 Formula

C16H19N3O4S

 Storage (From the date of receipt)
CAS No. 864814-88-0 Download SDF Storage of Stock Solutions

Synonyms RAS2410 Smiles CN(C)CC1=CC=C(C=C1)S(=O)(=O)N2C=CC(=C2)C=CC(=O)NO

Solubility

In vitro
Batch:

DMSO : 70 mg/mL (200.34 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 70 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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Mechanism of Action

Targets/IC50/Ki
HDAC1 [1]
42.5 nM
HDAC3 [1]
50.1 nM
HDAC6 [1]
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 this compound 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, this chemical 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. This compound decreases phosphorylation of 4E-BP1 and p70S6k indicating an interference with Akt pathway signalling. Treatment with this agent results in increased protein levels of Bim and Bax and decreases levels of Bcl-xL. Caspases 3, 8 and 9 are activated by it. Furthermore, synergistic effects are observed for combinations of this compound with melphalan and the proteasome inhibitors bortezomib and S-2209. [1]
Kinase Assay
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).
In vivo
Oral resminostat at 600 mg QD continuously d1−5 in a 14 day cycle is well-tolerated. This compound shows a favourable PK profile, with high bioavailability and low inter-pt variability. The apparent t 1/2 of this compound ranged from 2.7 to 4.4 hours. The modulation of plasma biomarkers further indicates drug activity. [2]
References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04955340 Completed
Cutaneous T Cell Lymphoma|Mycosis Fungoides|Sezary Syndrome
4SC AG
 October 12 2021 Phase 1
NCT01277406 Completed
Advanced Colorectal Carcinoma
4SC AG
 January 2011 Phase 1|Phase 2
NCT01037478 Completed
Hodgkin''s Lymphoma
4SC AG
 December 2009 Phase 2

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