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 ;
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.[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]

Clinical trials

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]

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.[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.

gollark: I just did, though.

gollark: Does "h" mean "I will immediately attain arbitrary quantities of money and donate it to osmarks.net for the purposes of hardware upgrades!"?

gollark: Of course, if you donate arbitrarily large amounts of money to osmarks.net, we can buy a T4 or RTX 3090 or P100 or something.

gollark: Colab can probably just about run GPT-J (6 billion parameters) unless they assign you a K80.

gollark: You could use NovelAI. It's a hosted service for GPTous text generation for fictional purposes. It does cost capital, though.

References

"Biological activity of resminostat in selleck chemicals research". selleck.
"4SC's Anti-Cancer Drug Resminostat achieves Median Overall Survival of 8.0 Months in Second-Line Advanced Liver Cancer (HCC) Patients". September 2012.
4SC 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. PMC 3790647. PMID 24065624.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[1] "Biological activity of resminostat in selleck chemicals research". selleck.

[2] "4SC's Anti-Cancer Drug Resminostat achieves Median Overall Survival of 8.0 Months in Second-Line Advanced Liver Cancer (HCC) Patients". September 2012.

[IND-2016-3] 4SC AG: FDA approves IND application for resminostat in liver cancer. Feb 2016

[4] 4SC-201 (Resminostat) in Advanced Colorectal Carcinoma (SHORE)

[5] Resminostat (4SC-201) in Relapsed or Refractory Hodgkin's Lymphoma (SAPHIRE)

[6] 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. PMC 3790647. PMID 24065624.