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Details

Stereochemistry ACHIRAL
Molecular Formula C22H25N3O3
Molecular Weight 379.4522
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of DACINOSTAT

SMILES

OCCN(CCC1=CNC2=CC=CC=C12)CC3=CC=C(\C=C\C(=O)NO)C=C3

InChI

InChIKey=BWDQBBCUWLSASG-MDZDMXLPSA-N
InChI=1S/C22H25N3O3/c26-14-13-25(12-11-19-15-23-21-4-2-1-3-20(19)21)16-18-7-5-17(6-8-18)9-10-22(27)24-28/h1-10,15,23,26,28H,11-14,16H2,(H,24,27)/b10-9+

HIDE SMILES / InChI

Molecular Formula C22H25N3O3
Molecular Weight 379.4522
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/15171259 | https://www.ncbi.nlm.nih.gov/pubmed/14529481 | https://www.ncbi.nlm.nih.gov/pubmed/15496978 | https://www.ncbi.nlm.nih.gov/pubmed/21073160

Dacinostat (also known as LAQ824), is a hydroxamate histone deacetylase inhibitor with potential anticancer activity. Dacinostat inhibits histone deacetylase enzymatic activities in vitro and transcriptionally activated the p21 promoter in reporter gene assays. Tumor cells treated with Dacinostat caused acetylation of HSP90 and degradation of its cargo oncoproteins. Flow cytometry studies revealed that both tumor cell lines and normal diploid fibroblasts arrested in the G2/M phase of the cell cycle after Dacinostat treatment. However, an increased sub-G1 population at 48 h (reminiscent of apoptotic cells) was only observed in the cancer cell lines treated with Dacinostat. Dacinostat exhibited antitumor effects in a xenograft animal models. In phase I trials, Dacinostat was well tolerated at doses that induced accumulation of histone acetylation, with higher doses inducing changes consistent with HSP90 inhibition. In another phase 1 in patients with advanced solid tumors, grade 3 or 4 toxicities were observed. Dacinostat had been in phase II clinical trials by Novartis for the treatment of solid tumors but further studies were discontinued.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
32.0 nM [IC50]
2.6 nM [IC50]
7.0 nM [IC50]
3.6 nM [IC50]
1.0 nM [IC50]
5.6 nM [IC50]
5.9 nM [IC50]
6.1 nM [IC50]
3.8 nM [IC50]
8.2 nM [IC50]
8.4 nM [IC50]
5.6 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Potentiation of the lethality of the histone deacetylase inhibitor LAQ824 by the cyclin-dependent kinase inhibitor roscovitine in human leukemia cells.
2005 Nov
The histone deacetylase inhibitor LAQ824 induces human leukemia cell death through a process involving XIAP down-regulation, oxidative injury, and the acid sphingomyelinase-dependent generation of ceramide.
2006 Jan
Antitumor effect of the histone deacetylase inhibitor LAQ824 in combination with 13-cis-retinoic acid in human malignant melanoma.
2007 Jan
The multikinase inhibitor sorafenib potentiates TRAIL lethality in human leukemia cells in association with Mcl-1 and cFLIPL down-regulation.
2007 Oct 1
Role of histone deacetylase inhibitor-induced reactive oxygen species and DNA damage in LAQ-824/fludarabine antileukemic interactions.
2008 Oct
Chemical phylogenetics of histone deacetylases.
2010 Mar
Optimization of the in vitro cardiac safety of hydroxamate-based histone deacetylase inhibitors.
2011 Jul 14
Patents

Sample Use Guides

LAQ824 (Dacinostat) was administered i.v. as a 3-h infusion on days 1, 2, and 3 every 21 days. The starting dose of 6 mg/m^2/d. Minimal toxicity was observed at the first five dose levels (6-48 mg/m^2/d); no dose-limiting toxicity was reported at the 6 and 12 mg/m^2/d dose levels.
Route of Administration: Intravenous
HCT-116 and NCI-H460 tumor cell lines were grown in a volume of 200 μL at approximately 10% confluency in 96-well multitier plates and were allowed to recover for an additional 24 h. Tumor cells were treated with either varying concentrations of Dacinostat or solvent for 24 h. After the cells had been treated, the plates were washed to remove drug and incubated for 48 h. The fraction of cells surviving after compound treatment was determined using the SRB assay.
Substance Class Chemical
Created
by admin
on Sat Dec 16 17:44:59 GMT 2023
Edited
by admin
on Sat Dec 16 17:44:59 GMT 2023
Record UNII
V10P524501
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DACINOSTAT
INN   WHO-DD  
INN  
Official Name English
NVP-LAQ824
Code English
LAQ-824
Common Name English
Dacinostat [WHO-DD]
Common Name English
dacinostat [INN]
Common Name English
LAQ824
Code English
(2E)-N-HYDROXY-3-(4-(((2-HYDROXYETHYL)(2-(1H-INDOL-3-YL)ETHYL)AMINO)METHYL)PHENYL)PROPENAMIDE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C1946
Created by admin on Sat Dec 16 17:44:59 GMT 2023 , Edited by admin on Sat Dec 16 17:44:59 GMT 2023
Code System Code Type Description
CAS
404951-53-7
Created by admin on Sat Dec 16 17:44:59 GMT 2023 , Edited by admin on Sat Dec 16 17:44:59 GMT 2023
PRIMARY
ChEMBL
CHEMBL356066
Created by admin on Sat Dec 16 17:44:59 GMT 2023 , Edited by admin on Sat Dec 16 17:44:59 GMT 2023
PRIMARY
EPA CompTox
DTXSID50870351
Created by admin on Sat Dec 16 17:44:59 GMT 2023 , Edited by admin on Sat Dec 16 17:44:59 GMT 2023
PRIMARY
FDA UNII
V10P524501
Created by admin on Sat Dec 16 17:44:59 GMT 2023 , Edited by admin on Sat Dec 16 17:44:59 GMT 2023
PRIMARY
NCI_THESAURUS
C81158
Created by admin on Sat Dec 16 17:44:59 GMT 2023 , Edited by admin on Sat Dec 16 17:44:59 GMT 2023
PRIMARY
PUBCHEM
6445533
Created by admin on Sat Dec 16 17:44:59 GMT 2023 , Edited by admin on Sat Dec 16 17:44:59 GMT 2023
PRIMARY
SMS_ID
100000127574
Created by admin on Sat Dec 16 17:44:59 GMT 2023 , Edited by admin on Sat Dec 16 17:44:59 GMT 2023
PRIMARY
EVMPD
SUB33618
Created by admin on Sat Dec 16 17:44:59 GMT 2023 , Edited by admin on Sat Dec 16 17:44:59 GMT 2023
PRIMARY
INN
8388
Created by admin on Sat Dec 16 17:44:59 GMT 2023 , Edited by admin on Sat Dec 16 17:44:59 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY