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Details

Stereochemistry ACHIRAL
Molecular Formula C21H23N3O5
Molecular Weight 397.4244
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ABEXINOSTAT

SMILES

CN(C)CC1=C(OC2=CC=CC=C12)C(=O)NCCOC3=CC=C(C=C3)C(=O)NO

InChI

InChIKey=MAUCONCHVWBMHK-UHFFFAOYSA-N
InChI=1S/C21H23N3O5/c1-24(2)13-17-16-5-3-4-6-18(16)29-19(17)21(26)22-11-12-28-15-9-7-14(8-10-15)20(25)23-27/h3-10,27H,11-13H2,1-2H3,(H,22,26)(H,23,25)

HIDE SMILES / InChI

Molecular Formula C21H23N3O5
Molecular Weight 397.4244
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 https://www.ncbi.nlm.nih.gov/pubmed/16731764

Abexinostat (PCI-24781) is a novel, second-generation phenyl hydroxamic acid–based, orally bioavailable HDAC inhibitor that has previously been shown to have activity in vitro and in vivo against a broad array of cancers, including hematopoietic malignancies and bone and soft-tissue sarcomas. Abexinostat is a pan-HDAC inhibitor mostly targeting HDAC1 with Ki of 7 nM, modest potent to HDACs 2, 3, 6, and 10 and greater than 40-fold selectivity against HDAC8. Abexinostat exhibits potent antitumor activity against a variety of tumor cell lines with GI50 ranging from 0.15 uM to 3.09 uM. PCI-24781 also has an antiproliferative effect on HUVEC endothelial cells with GI50 of 0.43 uM. Abexinostat treatment causes dose-dependent accumulation of both acetylated histones and acetylated tubulin in HCT116 or DLD-1 cells, induces expression of p21, and leads to PARP cleavage and accumulation of the γH2AX. It has also shown good tolerability and activity in Phase I and II clinical trials against lymphoma, as well as against solid tumors in Phase-I trials. Additionally, it acts as a potent radiosensitizing agent and is synergistic with cytotoxic chemotherapy, such as doxorubicin in preclinical models.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
7.0 nM [Ki]
8.2 nM [Ki]
17.0 nM [Ki]
19.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
CRA-024781: a novel synthetic inhibitor of histone deacetylase enzymes with antitumor activity in vitro and in vivo.
2006 May
PCI-24781 induces caspase and reactive oxygen species-dependent apoptosis through NF-kappaB mechanisms and is synergistic with bortezomib in lymphoma cells.
2009 May 15
Deactylase inhibition in myeloproliferative neoplasms.
2010 Dec
Vorinostat in acute myeloid leukemia and myelodysplastic syndromes.
2011 Feb
Patents

Patents

Sample Use Guides

Dose Escalation: Up to 5 cohorts will receive Abexinostat (PCI-24781) orally at doses starting at 30mg/m2 two times a day approximately 4-6 hours apart ("BID"), up to 90mg/m2 administered 5 days/week during the first 21 days of each 28 day cycle until the maximum tolerated dose (MTD) is reached. If a dose limiting toxicity (DLT) occurs, then the next cohort will receive Abexinostat (PCI-24781) BID for 7 days every other week (2 times in a 28 day cycle).
Route of Administration: Oral
inhibited pure recombinant HDAC1 with a K(i) of 0.007 umol/L, and also inhibited the other HDAC isozymes HDAC2, HDAC3/SMRT, HDAC6, HDAC8, and HDAC10 in the nanomolar range.
Substance Class Chemical
Created
by admin
on Fri Dec 15 18:17:31 GMT 2023
Edited
by admin
on Fri Dec 15 18:17:31 GMT 2023
Record UNII
IYO470654U
Record Status Validated (UNII)
Record Version
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Name Type Language
ABEXINOSTAT
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
S-78454
Code English
PCI-24781
Code English
CRA-024781
Code English
CRA 24781
Code English
PCI 24781
Code English
abexinostat [INN]
Common Name English
ABEXINOSTAT [USAN]
Common Name English
PZP115891
Code English
Abexinostat [WHO-DD]
Common Name English
2-BENZOFURANCARBOXAMIDE, 3-((DIMETHYLAMINO)METHYL)-N-(2-(4-((HYDROXYAMINO)CARBONYL)PHENOXY)ETHYL)-
Systematic Name English
3-((DIMETHYLAMINO)METHYL)-N-(2-(4-(HYDROXYCARBAMOYL)PHENOXY)ETHYL)-1-BENZOFURAN-2-CARBOXAMIDE
Systematic Name English
S78454
Code English
PZP-115891
Code English
CRA 024781
Code English
Classification Tree Code System Code
NCI_THESAURUS C1946
Created by admin on Fri Dec 15 18:17:31 GMT 2023 , Edited by admin on Fri Dec 15 18:17:31 GMT 2023
Code System Code Type Description
USAN
XX-82
Created by admin on Fri Dec 15 18:17:31 GMT 2023 , Edited by admin on Fri Dec 15 18:17:31 GMT 2023
PRIMARY
EPA CompTox
DTXSID30229005
Created by admin on Fri Dec 15 18:17:31 GMT 2023 , Edited by admin on Fri Dec 15 18:17:31 GMT 2023
PRIMARY
FDA UNII
IYO470654U
Created by admin on Fri Dec 15 18:17:31 GMT 2023 , Edited by admin on Fri Dec 15 18:17:31 GMT 2023
PRIMARY
CAS
783355-60-2
Created by admin on Fri Dec 15 18:17:31 GMT 2023 , Edited by admin on Fri Dec 15 18:17:31 GMT 2023
PRIMARY
DRUG BANK
DB12565
Created by admin on Fri Dec 15 18:17:31 GMT 2023 , Edited by admin on Fri Dec 15 18:17:31 GMT 2023
PRIMARY
PUBCHEM
11749858
Created by admin on Fri Dec 15 18:17:31 GMT 2023 , Edited by admin on Fri Dec 15 18:17:31 GMT 2023
PRIMARY
NCI_THESAURUS
C68920
Created by admin on Fri Dec 15 18:17:31 GMT 2023 , Edited by admin on Fri Dec 15 18:17:31 GMT 2023
PRIMARY
WIKIPEDIA
ABEXINOSTAT
Created by admin on Fri Dec 15 18:17:31 GMT 2023 , Edited by admin on Fri Dec 15 18:17:31 GMT 2023
PRIMARY
INN
9422
Created by admin on Fri Dec 15 18:17:31 GMT 2023 , Edited by admin on Fri Dec 15 18:17:31 GMT 2023
PRIMARY
SMS_ID
100000174900
Created by admin on Fri Dec 15 18:17:31 GMT 2023 , Edited by admin on Fri Dec 15 18:17:31 GMT 2023
PRIMARY
ChEMBL
CHEMBL2103863
Created by admin on Fri Dec 15 18:17:31 GMT 2023 , Edited by admin on Fri Dec 15 18:17:31 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Abexinostat (PCI-24781) is a modestly potent inhibitor to HDAC3. Phase 1/2.
INHIBITOR
MODERATE
TARGET -> INHIBITOR
Abexinostat (PCI-24781) is a modestly potent inhibitor to HDAC2. Phase 1/2.
INHIBITOR
MODERATE
TARGET -> INHIBITOR
Abexinostat (PCI-24781) is a novel pan-HDAC inhibitor mostly targeting HDAC1 with Ki of 7 NM. Phase 1/2.
INHIBITOR
Ki
CONSTITUENT ALWAYS PRESENT -> PARENT
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
Abexinostat (PCI-24781) is a modestly potent inhibitor to HDA6. Phase 1/2.
INHIBITOR
MODERATE
TARGET -> INHIBITOR
Abexinostat (PCI-24781) is a modestly potent inhibitor to HDAC10. Phase 1/2.
INHIBITOR
MODERATE
Related Record Type Details
ACTIVE MOIETY