Resminostat

Resminostat

Names
IUPAC name (2E)-3-[1-({4-[(Dimethylamino)methyl]phenyl}sulfonyl)-1H-pyrrol-3-yl]-N-hydroxyacrylamide
Other names RAS2410; Resminostat 4SC-201
Identifiers
CAS Number	864814-88-0
3D model (JSmol)	Interactive image
ChemSpider	9784710
IUPHAR/BPS	7502
PubChem CID	11609955
UNII	1578EUB98L Y
CompTox Dashboard (EPA)	DTXSID50235587
InChI 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+ Key: FECGNJPYVFEKOD-VMPITWQZSA-N InChI=1/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+ Key: FECGNJPYVFEKOD-VMPITWQZBF
SMILES CN(C)CC1=CC=C(C=C1)S(=O)(=O)N2C=CC(=C2)/C=C/C(=O)NO
Properties
Chemical formula	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). Infobox references

Resminostat (4SC-201 or RAS2410) is an orally bioavailable inhibitor of histone deacetylases (HDACs), of which inhibitors are antineoplastic agents.
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).

In 2016 the FDA granted [another?] IND for clinical tests in combination with sorafenib for HCC. 4SC say "In several phase I and phase II trials, resminostat has already demonstrated very good safety and tolerability, alongside promising indications of efficacy."

Clinical trials

It has undergone a phase I/II clinical trial for K-ras mutated advanced colorectal carcinoma.

It has undergone a phase II clinical trial for relapsed or refractory Hodgkin's Lymphoma.

Mechanism

Resminostat restrains the phosphorylation of 4E-BP1 and p70S6k, indicating an disturbance with Akt signalling pathway. The treatment of resminostat leads to a drop of Bim and Bax protein level and Bcl-xL level.

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.