U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of Givinostat hydrochloride anhydrous

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

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C24H27N3O4
Molecular Weight 421.4889
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
28.0 nM [EC50]
56.0 nM [EC50]
21.0 nM [EC50]
52.0 nM [EC50]
27.0 nM [EC50]
163.0 nM [EC50]
Conditions
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
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

up to 12 weeks at a dosage of 1.5 mg/kg/day
Route of Administration: Oral
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.
Substance Class Chemical
Created
by admin
on Sat Dec 16 01:51:52 GMT 2023
Edited
by admin
on Sat Dec 16 01:51:52 GMT 2023
Record UNII
Z02132R2QQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
Givinostat hydrochloride anhydrous
Common Name English
Carbamic acid, N-[4-[(hydroxyamino)carbonyl]phenyl]-, [6-[(diethylamino)methyl]-2-naphthalenyl]methyl ester, hydrochloride (1:1)
Systematic Name English
ITF2357 Hydrochloride
Code English
ITF-2357 Hydrochloride
Code English
[6-[(Diethylamino)methyl]-2-naphthalenyl]methyl N-[4-[(hydroxyamino)carbonyl]phenyl]carbamate hydrochloride (1:1)
Systematic Name English
Code System Code Type Description
PUBCHEM
10095659
Created by admin on Sat Dec 16 01:51:53 GMT 2023 , Edited by admin on Sat Dec 16 01:51:53 GMT 2023
PRIMARY
FDA UNII
Z02132R2QQ
Created by admin on Sat Dec 16 01:51:53 GMT 2023 , Edited by admin on Sat Dec 16 01:51:53 GMT 2023
PRIMARY
EPA CompTox
DTXSID90941872
Created by admin on Sat Dec 16 01:51:53 GMT 2023 , Edited by admin on Sat Dec 16 01:51:53 GMT 2023
PRIMARY
SMS_ID
100000175511
Created by admin on Sat Dec 16 01:51:53 GMT 2023 , Edited by admin on Sat Dec 16 01:51:53 GMT 2023
PRIMARY
CAS
199657-29-9
Created by admin on Sat Dec 16 01:51:53 GMT 2023 , Edited by admin on Sat Dec 16 01:51:53 GMT 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
SOLVATE->ANHYDROUS
Related Record Type Details
ACTIVE MOIETY