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Details

Stereochemistry ACHIRAL
Molecular Formula C21H23N3O5.C7H8O3S
Molecular Weight 569.626
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ABEXINOSTAT TOSYLATE

SMILES

CC1=CC=C(C=C1)S(O)(=O)=O.CN(C)CC2=C(OC3=CC=CC=C23)C(=O)NCCOC4=CC=C(C=C4)C(=O)NO

InChI

InChIKey=XMXZUHOHUKWCJK-UHFFFAOYSA-N
InChI=1S/C21H23N3O5.C7H8O3S/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;1-6-2-4-7(5-3-6)11(8,9)10/h3-10,27H,11-13H2,1-2H3,(H,22,26)(H,23,25);2-5H,1H3,(H,8,9,10)

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

Molecular Formula C7H8O3S
Molecular Weight 172.202
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
Deactylase inhibition in myeloproliferative neoplasms.
2010 Dec
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 Thu Jul 06 21:16:26 UTC 2023
Edited
by admin
on Thu Jul 06 21:16:26 UTC 2023
Record UNII
AOH3JC92C0
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ABEXINOSTAT TOSYLATE
Common Name English
2-BENZOFURANCARBOXAMIDE, 3-((DIMETHYLAMINO)METHYL)-N-(2-(4-((HYDROXYAMINO)CARBONYL)PHENOXY)ETHYL)-, 4-METHYLBENZENESULFONATE (1:1)
Systematic Name English
Code System Code Type Description
NCI_THESAURUS
C160889
Created by admin on Thu Jul 06 21:16:26 UTC 2023 , Edited by admin on Thu Jul 06 21:16:26 UTC 2023
PRIMARY
SMS_ID
100000183701
Created by admin on Thu Jul 06 21:16:26 UTC 2023 , Edited by admin on Thu Jul 06 21:16:26 UTC 2023
PRIMARY
PUBCHEM
77461142
Created by admin on Thu Jul 06 21:16:26 UTC 2023 , Edited by admin on Thu Jul 06 21:16:26 UTC 2023
PRIMARY
FDA UNII
AOH3JC92C0
Created by admin on Thu Jul 06 21:16:26 UTC 2023 , Edited by admin on Thu Jul 06 21:16:26 UTC 2023
PRIMARY
CAS
1622385-42-5
Created by admin on Thu Jul 06 21:16:26 UTC 2023 , Edited by admin on Thu Jul 06 21:16:26 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
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ACTIVE MOIETY