Names | |
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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 | |
Identifiers | |
3D model (JSmol) | |
ChemSpider | |
PubChem CID | |
UNII | |
CompTox Dashboard (EPA) | |
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Properties | |
C16H19N3O4S | |
Molar mass | 349.41 g·mol−1 |
Density | 1.282 g/cm3 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Resminostat (4SC-201 or RAS2410) is an orally bioavailable inhibitor of histone deacetylases (HDACs), of which inhibitors are antineoplastic agents. [1]
In 2011, the German drug maker 4SC was granted orphan drug designation for resminostat by the US FDA for the treatment of hepatocellular carcinoma (HCC). [2]
In 2016 the FDA granted [another?] IND for clinical tests in combination with sorafenib for 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]
It has undergone a phase I/II clinical trial for K-ras mutated advanced colorectal carcinoma. [4]
It has undergone a phase II clinical trial for relapsed or refractory Hodgkin's Lymphoma. [5]
Resminostat restrains the phosphorylation of 4E-BP1 and p70S6k, indicating a disturbance with Akt signalling pathway. The treatment of resminostat leads to a drop of Bim and Bax protein level and Bcl-xL level. [6]
As with other HDAC inhibitors such as pracinostat, the inhibition of HDACs by resminostat results in an accumulation of highly acetylated histones, followed by an abduction of chromatin remodeling, inhibition of tumor suppressor genes transcription and cell division, and finally tumor cell apoptosis.
Tipifarnib is a farnesyltransferase inhibitor. Farnesyltransferase inhibitors block the activity of the farnesyltransferase enzyme by inhibiting prenylation of the CAAX tail motif, which ultimately prevents Ras from binding to the membrane, rendering it inactive.
Vorinostat (rINN) also known as Suberoylanilide hydroxamic acid is a member of a larger class of compounds that inhibit histone deacetylases (HDAC). Histone deacetylase inhibitors (HDI) have a broad spectrum of epigenetic activities.
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Romidepsin, also known as Istodax, is an anticancer agent used in cutaneous T-cell lymphoma (CTCL) and other peripheral T-cell lymphomas (PTCLs). Romidepsin is a natural product obtained from the bacterium Chromobacterium violaceum, and works by blocking enzymes known as histone deacetylases, thus inducing apoptosis. It is sometimes referred to as depsipeptide, after the class of molecules to which it belongs. Romidepsin is branded and owned by Gloucester Pharmaceuticals, now a part of Celgene.
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Crizotinib, sold under the brand name Xalkori among others, is an anti-cancer medication used for the treatment of non-small cell lung carcinoma (NSCLC). It acts as an ALK and ROS1 inhibitor.
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