CITARINOSTAT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H26ClN5O3
Molecular Weight	467.948
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

ONC(=O)CCCCCCNC(=O)C1=CN=C(N=C1)N(C2=CC=CC=C2)C3=C(Cl)C=CC=C3

InChI

InChIKey=VLIUIBXPEDFJRF-UHFFFAOYSA-N

InChI=1S/C24H26ClN5O3/c25-20-12-7-8-13-21(20)30(19-10-4-3-5-11-19)24-27-16-18(17-28-24)23(32)26-15-9-2-1-6-14-22(31)29-33/h3-5,7-8,10-13,16-17,33H,1-2,6,9,14-15H2,(H,26,32)(H,29,31)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27926524 | https://clinicaltrials.gov/ct2/show/NCT02551185

HDAC-IN-2 (also known as citarinostat or ACY-241) was developed as a selective histone deacetylase (HDAC) 6 inhibitor with potential antineoplastic activity. Inhibition of HDAC leads to the inhibition of tumor oncogene transcription, and the selective transcription of tumor suppressor genes, which inhibit tumor cell division and induce tumor cell apoptosis. HDAC-IN-2 participates in phase 1b clinical trial in patients with multiple myeloma to determine the maximum tolerated dose (MTD) and evaluate the safety and preliminary antitumor activity. Besides, HDAC-IN-2 in combination with paclitaxel participates in phase Ib in patients with advanced solid tumors. In addition, HDAC-IN-2 in combination with nivolumab participates in phase I in patients with unresectable non-small cell lung cancer to determine the safety, tolerability, dose-limiting toxicities (DLTs), and maximum tolerated dose (MTD) of the drug.

Approval Year

Targets

Primary Target	Pharmacology	Potency
Histone deacetylase 6 27 Target ID: CHEMBL1865 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27926524	Inhibitor 8297	2.6 nM [IC50]
Histone deacetylase 1 51 Target ID: CHEMBL325 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27926524	Inhibitor 8297	35.0 nM [IC50]
Histone deacetylase 2 37 Target ID: CHEMBL1937 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27926524	Inhibitor 8297	45.0 nM [IC50]
Histone deacetylase 3 35 Target ID: CHEMBL1829 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27926524	Inhibitor 8297	46.0 nM [IC50]
Histone deacetylase 8 17 Target ID: CHEMBL3192 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27926524	Inhibitor 8297	137.0 nM [IC50]

PubMed

Title	Date	PubMed
Selective HDAC inhibition by ACY-241 enhances the activity of paclitaxel in solid tumor models.	2017 Jan 10	27926524

Sample Use Guides

In Vivo Use Guide

Open label dosing cohorts will evaluate oral ACY-241 (HDAC-IN-2) (dosing ranging from 180 mg to 480 mg days 1-21) in combination with oral pomalidomide (4 mg days 1-21), and oral dexamethasone (40 mg qd on days 1, 8, 15, 22).

Route of Administration: Oral

Name

Type

Language

CITARINOSTAT

Official Name

English

5-PYRIMIDINECARBOXAMIDE, 2-((2-CHLOROPHENYL)PHENYLAMINO)-N-(7-(HYDROXYAMINO)-7-OXOHEPTYL)-

Systematic Name

English

CITARINOSTAT [USAN]

Common Name

English

2-((2-CHLOROPHENYL)PHENYLAMINO)-N-(7-(HYDROXYAMINO)-7-OXOHEPTYL)-5-PYRIMIDINECARBOXAMIDE

Systematic Name

English

citarinostat [INN]

Common Name

English

2-[(2-Chlorophenyl)phenylamino]-N-[7-(hydroxyamino)-7-oxoheptyl]pyrimidine-5-carboxamide

Systematic Name

English

Citarinostat [WHO-DD]

Common Name

English

HDAC-IN-2

Code

English

ACY-241

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1946