ABEXINOSTAT TOSYLATE

Investigational

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 Search

SMILES

CC1=CC=C(C=C1)S(O)(=O)=O.CN(C)CC2=C(OC3=C2C=CC=C3)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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25520806
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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Histone deacetylase 1 51 Target ID: CHEMBL325 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16731764	Inhibitor 8504	7.0 nM [Ki]
Histone deacetylase 3 35 Target ID: CHEMBL1829 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16731764	Inhibitor 8504	8.2 nM [Ki]
Histone deacetylase 6 28 Target ID: CHEMBL1865 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16731764	Inhibitor 8504	17.0 nM [Ki]
Histone deacetylase 2 37 Target ID: CHEMBL1937 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16731764	Inhibitor 8504	19.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Sarcoma 14 Sources: https://clinicaltrials.gov/ct2/show/NCT01027910	Primary		Phase II 1147	Unknown Approved Use Unknown
Lymphoma 60 Sources: https://clinicaltrials.gov/ct2/show/NCT00724984	Primary		Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
277 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27911138	120 mg 2 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ABEXINOSTAT blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1130 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27911138	120 mg 2 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ABEXINOSTAT blood	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741

Drug as perpetrator

Target	Modality	Activity
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363677421	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363677421	yes [IC50 1.6933 uM]
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363677421	yes [IC50 4.6109 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363677421	yes [IC50 9.5221 uM]

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY110881	https://www.001chemical.com/chem/search?q=DY110881
1PlusChem LLC	1P00G464	https://www.1pchem.com/search?query=1P00G464
AK Scientific	X7604	https://aksci.com/item_detail.php?cat=X7604
Angene	AGN-PC-00FE5D	http://www.angenechemical.com/productshow/AGN-PC-00FE5D.html
ApexBio Technology	A4098	https://www.apexbt.com/catalogsearch/result/?q=A4098
AstaTech	FD5037	http://astatechinc.com/CPSResult.php?CRNO=FD5037
BLD Pharm	BD304661	http://www.bldpharm.com/search/Search.html?keyword=BD304661
Cayman Chemical	20059	http://www.caymanchem.com/app/template/Product.vm/catalog/20059
Chem Scene	CS-0478	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0478
ChemShuttle	101138	https://www.chemshuttle.com/catalogsearch/result/?q=101138
Debye Scientific	DB-075461	https://www.debyesci.com/index.php?id=product&ext[cno]=DB-075461
eMolecules	36516757	https://orderbb.emolecules.com/search/#?query=36516757
Enamine	EN300-204651	https://www.enaminestore.com/catalog/EN300-204651
eNovation Chemicals	D501879	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501879&searchbtn.x=0&searchbtn.y=0
Excenen	EX-A2123	http://www.excenen.com/searchresultlist.php?id=EX-A2123
Exclusive Chemistry	2348	http://www.exchemistry.com/chem-catalog/product-2348.html
Lab Network	LN01304296	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01304296
Matrix Scientific	143798	http://www.matrixscientific.com/143798.html
mcule	MCULE-8321862364	https://mcule.com/MCULE-8321862364/
MedChem Express	HY-10990	https://www.medchemexpress.com/search.html?q=HY-10990&ft=&fa=&fp=
Molcore	MC110881	http://www.molcore.com/CatMC110881.html
Molnova	M15956	https://www.molnova.com/en/serch-list.html?keywords=M15956
MolPort	MolPort-016-633-175	https://www.molport.com/shop/molecule-link/MolPort-016-633-175
Ryan Scientific	PI3065	https://ryansci.com/products?q=PI3065&list_q=&search_type=exact
ShangHai Biochempartner	BCP000140	http://www.biochempartner.com/search_BCP000140
ShangHai Biochempartner	BCP01840	http://www.biochempartner.com/search_BCP01840
Synthonix	SL101124	http://www.synthon-lab.com/search.php?cas_or_id=SL101124&cas_id_field=1
TargetMol	T0431	https://www.targetmol.com/search?keyword=T0431
Toronto Research Chemicals	P216400	https://www.trc-canada.com/product-detail/?CatNum=P216400

PubMed

Title	Date	PubMed
CRA-024781: a novel synthetic inhibitor of histone deacetylase enzymes with antitumor activity in vitro and in vivo.	2006 May	16731764
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	19417023
Deactylase inhibition in myeloproliferative neoplasms.	2010 Dec	21127942
A novel histone deacetylase inhibitor Chidamide induces apoptosis of human colon cancer cells.	2010 Feb 5	20060381
Vorinostat in acute myeloid leukemia and myelodysplastic syndromes.	2011 Feb	21192773

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 `Wed Apr 02 06:38:16 GMT 2025` Edited by `admin` on `Wed Apr 02 06:38:16 GMT 2025`
Record UNII	AOH3JC92C0
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ABEXINOSTAT TOSYLATE

Common Name

English

2-BENZOFURANCARBOXAMIDE, 3-((DIMETHYLAMINO)METHYL)-N-(2-(4-((HYDROXYAMINO)CARBONYL)PHENOXY)ETHYL)-, 4-METHYLBENZENESULFONATE (1:1)

Preferred Name

English

Code System Code Type Description

NCI_THESAURUS

C160889