Details
Stereochemistry | ACHIRAL |
Molecular Formula | C24H27N3O4.ClH |
Molecular Weight | 457.95 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.CCN(CC)CC1=CC=C2C=C(COC(=O)NC3=CC=C(C=C3)C(=O)NO)C=CC2=C1
InChI
InChIKey=QKSGNWJOQMSBEP-UHFFFAOYSA-N
InChI=1S/C24H27N3O4.ClH/c1-3-27(4-2)15-17-5-7-21-14-18(6-8-20(21)13-17)16-31-24(29)25-22-11-9-19(10-12-22)23(28)26-30;/h5-14,30H,3-4,15-16H2,1-2H3,(H,25,29)(H,26,28);1H
DescriptionCurator's Comment: description was created based on several sources, including:
http://adisinsight.springer.com/drugs/800023261 | https://newdrugapprovals.org/2015/03/05/givinostat/ | https://en.wikipedia.org/wiki/Givinostat
Curator's Comment: description was created based on several sources, including:
http://adisinsight.springer.com/drugs/800023261 | https://newdrugapprovals.org/2015/03/05/givinostat/ | https://en.wikipedia.org/wiki/Givinostat
Gavinostat is an orally bioavailable hydroxymate inhibitor of histone deacetylase (HDAC) with potential anti-inflammatory, anti-angiogenic, and antineoplastic activities. Gavinostat inhibits class I and class II HDACs, resulting in an accumulation of highly acetylated histones, followed by the induction of chromatin remodeling and an altered pattern of gene expression. At low, nonapoptotic concentrations, this agent inhibits the production of pro-inflammatory cytokines such as tumor necrosis factor- (TNF-), interleukin-1 (IL-1), IL-6 and interferon-gamma. It is currently in phase 2 trials for Myeloproliferative disorders, Polycythaemia vera and Phase III for Duchenne muscular dystrophy announced. In clinical trials of givinostat as a salvage therapy for advanced Hodgkin's lymphoma, the most common adverse reactions were fatigue, mild diarrhea or abdominal pain, moderate thrombocytopenia, and mild leukopenia.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL325 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17868033 |
28.0 nM [EC50] | ||
Target ID: CHEMBL1937 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17868033 |
56.0 nM [EC50] | ||
Target ID: CHEMBL1829 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17868033 |
21.0 nM [EC50] | ||
Target ID: CHEMBL3524 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17868033 |
52.0 nM [EC50] | ||
Target ID: CHEMBL1865 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17868033 |
27.0 nM [EC50] | ||
Target ID: CHEMBL2716 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17868033 |
163.0 nM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
---|---|---|
Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors. | 2008 Jan 15 |
|
Chemical phylogenetics of histone deacetylases. | 2010 Mar |
|
The histone deacetylase inhibitor ITF2357 decreases surface CXCR4 and CCR5 expression on CD4(+) T-cells and monocytes and is superior to valproic acid for latent HIV-1 expression in vitro. | 2010 May 1 |
|
Optimization of the in vitro cardiac safety of hydroxamate-based histone deacetylase inhibitors. | 2011 Jul 14 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21538322
up to 12 weeks at a dosage of 1.5 mg/kg/day
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16557334
ITF2357 at 100 nM reduced LPS-induced GM-CSF by 99% and 89%, respectively. However, when stimulated with anti-CD3, there was no reduction in GM-CSF by ITF2357 at 37 or 100 nM.
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ACTIVE MOIETY
SUBSTANCE RECORD