Resminostat
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| Preferred IUPAC name
(2E)-3-(1-{4-[(Dimethylamino)methyl]benzene-1-sulfonyl}-1H-pyrrol-3-yl)-N-hydroxyprop-2-enamide | |
| Other names
RAS2410; Resminostat 4SC-201
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| Identifiers | |
3D model (JSmol)
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| ChEBI | |
| ChemSpider | |
PubChemCID
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| UNII | |
CompTox Dashboard(EPA)
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| Properties | |
| C16H19N3O4S | |
| Molar mass | 349.41g·mol−1 |
| Density | 1.282 g/cm3 |
| Pharmacology | |
| None | |
Except where otherwise noted, data are given for materials in theirstandard state(at 25 °C [77 °F], 100 kPa).
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Resminostat(4SC-201orRAS2410) is an orally bioavailable inhibitor ofhistone deacetylases(HDACs), of which inhibitors areantineoplastic agents.[1]
In 2011, the German drug maker 4SC was grantedorphan drugdesignation for resminostat by theUS FDAfor the treatment ofhepatocellular carcinoma(HCC).[2]
In 2016, the FDA grantedINDfor clinical tests in combination withsorafenibfor HCC.[3]4SC say "In several phase I and phase II trials, resminostat has already demonstrated very good safety and tolerability, alongside promising indications of efficacy."[3]
Clinical trials
[edit]Resminostat has undergone a phase I/II clinical trial for K-ras mutated advancedcolorectal carcinoma.[4]
It has undergone a phase II clinical trial for relapsed or refractoryHodgkin's lymphoma.[5]
Mechanism
[edit]Resminostat restrains thephosphorylationof4E-BP1andp70S6k,indicating a disturbance withAkt signalling pathway.The treatment of resminostat leads to a drop of Bim andBaxprotein level andBcl-xLlevel.[6]
As with otherHDAC inhibitorssuch aspracinostat,the inhibition of HDACs by resminostat results in an accumulation of highly acetylatedhistones,followed by an abduction ofchromatin remodeling,inhibition of tumor suppressorgenes transcriptionandcell division,and finally tumorcell apoptosis.
References
[edit]- ^Tsilimigras, D. I.; Ntanasis-Stathopoulos, I.; Moris, D.; Spartalis, E.; Pawlik, T. M. (2018)."Histone deacetylase inhibitors in hepatocellular carcinoma: A therapeutic perspective".Surgical Oncology.27(4). Elsevier Surg Oncol 2018 Dec;27(4):611-618.doi: 10.1016/j.suronc.2018.07.015.Epub 2018 Jul 30.: 611–618.doi:10.1016/j.suronc.2018.07.015.PMID30449480.S2CID53947365.
- ^"4SC's Anti-Cancer Drug Resminostat achieves Median Overall Survival of 8.0 Months in Second-Line Advanced Liver Cancer (HCC) Patients".September 2012.
- ^ab4SC AG: FDA approves IND application for resminostat in liver cancer. Feb 2016
- ^4SC-201 (Resminostat) in Advanced Colorectal Carcinoma (SHORE)
- ^Resminostat (4SC-201) in Relapsed or Refractory Hodgkin's Lymphoma (SAPHIRE)
- ^Brunetto AT, et al. (1 Oct 2013)."First-in-human, pharmacokinetic and pharmacodynamic phase I study of Resminostat, an oral histone deacetylase inhibitor, in patients with advanced solid tumors".Clin Cancer Res.19(19): 5494–504.doi:10.1158/1078-0432.CCR-13-0735.PMC3790647.PMID24065624.