Abexinostat

Summary

Abexinostat (CHEMBL2103863) is a phase-3 clinical-stage small-molecule EC 3.5.1.98 (histone deacetylase) inhibitor targeting HDAC3 and HDAC1; indicated across 7 conditions including renal cell carcinoma and diffuse large b-cell lymphoma; with CIViC clinical evidence for 1 variant-indication association (e.g. HDAC2 Expression in renal cell carcinoma).

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 2 (HDAC3, HDAC1)
• Indications: 7 conditions
• Clinical trials: 14
• Precision-oncology evidence (CIViC): 1 variant–indication association
• Chemistry: 397.4 Da · C21H23N3O5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2103863
Name	Abexinostat
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	11749858
ChEBI	CHEBI:92223
Molecular formula	C21H23N3O5
Molecular weight	397.4
InChIKey	MAUCONCHVWBMHK-UHFFFAOYSA-N

SMILES: CN(C)CC1=C(OC2=CC=CC=C21)C(=O)NCCOC3=CC=C(C=C3)C(=O)NO

IUPAC name: 3-[(dimethylamino)methyl]-N-[2-[4-(hydroxycarbamoyl)phenoxy]ethyl]-1-benzofuran-2-carboxamide

ChEBI definition: A 1-benzofuran substituted by {2-[4-(hydroxycarbamoyl)phenoxy]ethyl}aminocarbonyl and (dimethylamino)methyl groups at positions 2 and 3, respectively. It is a potent pan-HDAC inhibitor whose major target is HDAC1 (Ki = 7 nM).

Pharmacological roles (ChEBI): EC 3.5.1.98 (histone deacetylase) inhibitor, antineoplastic agent, apoptosis inducer, radiosensitizing agent, autophagy inducer.

Also known as: Abexinostat, CRA 024781, CRA 24781, CRA-024781, PCI 24781, PCI-24781, PZP-115891, PZP115891, S-78454, S78454, ABEXINOSTAT, ABEXINOSTAT (PCI-24781)

Parent form; salt/anhydrous children: CHEMBL2105727

Patent coverage: 818 distinct patent families (2,195 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 2,184 (99%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
HDAC3	histone deacetylase 3	Inhibition	8.09	95.1% (common-essential)	O15379
HDAC1	histone deacetylase 1	Inhibition	8.15	4.5%	Q13547

Broader ChEMBL bioactivity targets: 12 (assay-derived). Sample: Histone deacetylase 3, Protein deacetylase HDAC6, Histone deacetylase 2, Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2), Histone deacetylase 5, Histone deacetylase 7, Histone deacetylase 8, Histone deacetylase 1, Histone deacetylase 11, Histone deacetylase 4.

Bioactivity

ChEMBL activities: 30 potent at pChembl ≥ 5 of 30 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HDAC10	8.4	IC50	3.98	nM	CHEMBL_ACT_19177254
HDAC1	8.15	Ki	7	nM	CHEMBL_ACT_15656402
HDAC1	8.15	IC50	7	nM	CHEMBL_ACT_25573746
HDAC10	8.1	IC50	7.94	nM	CHEMBL_ACT_19177283
HDAC3	8.09	Ki	8.2	nM	CHEMBL_ACT_15656382
HDAC1	8	Ki	10	nM	CHEMBL_ACT_18157072
HDAC3	8	Ki	10	nM	CHEMBL_ACT_18157083
HDAC3	8	IC50	10.1	nM	CHEMBL_ACT_25573874
HDAC6	7.92	IC50	12	nM	CHEMBL_ACT_22974835
HDAC11	7.85	IC50	14	nM	CHEMBL_ACT_22974843
HDAC6	7.77	Ki	17	nM	CHEMBL_ACT_15656471
HDAC2	7.72	Ki	19	nM	CHEMBL_ACT_15656392
HDAC6	7.72	IC50	19.1	nM	CHEMBL_ACT_25573880
HDAC2	7.7	Ki	20	nM	CHEMBL_ACT_18157078
HDAC6	7.7	Ki	20	nM	CHEMBL_ACT_18157098
HDAC10	7.7	Ki	20	nM	CHEMBL_ACT_18157119
HDAC1	7.68	IC50	21	nM	CHEMBL_ACT_22974819
HDAC10	7.62	Ki	24	nM	CHEMBL_ACT_15656476
HDAC2	7.41	IC50	39.2	nM	CHEMBL_ACT_25573872
HDAC5	7.32	IC50	48	nM	CHEMBL_ACT_22974829
HDAC10	7.28	IC50	52	nM	CHEMBL_ACT_22974837
HDAC4	7.22	IC50	60	nM	CHEMBL_ACT_22974827
HDAC2	7.2	IC50	63	nM	CHEMBL_ACT_22974821
HDAC6	7.14	IC50	72.19	nM	CHEMBL_ACT_23140981
HDAC3	6.83	IC50	148	nM	CHEMBL_ACT_22974823
HDAC9	6.78	IC50	168	nM	CHEMBL_ACT_22974833
HDAC8	6.55	Ki	280	nM	CHEMBL_ACT_15656427
HDAC8	6.55	Ki	280	nM	CHEMBL_ACT_18157109
HDAC7	6.46	IC50	350	nM	CHEMBL_ACT_22974831
HDAC8	6.43	IC50	370	nM	CHEMBL_ACT_22974825

Target pathways

Aggregated over 2 target gene(s): HDAC3, HDAC1.

Top Reactome pathways

57 total, by targets touching each:

Pathway	Targets	Genes
p75NTR negatively regulates cell cycle via SC1	2	HDAC1, HDAC3
NOTCH1 Intracellular Domain Regulates Transcription	2	HDAC1, HDAC3
Constitutive Signaling by NOTCH1 PEST Domain Mutants	2	HDAC1, HDAC3
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	2	HDAC1, HDAC3
HDACs deacetylate histones	2	HDAC1, HDAC3
Notch-HLH transcription pathway	2	HDAC1, HDAC3
Regulation of PTEN gene transcription	2	HDAC1, HDAC3
Regulation of MECP2 expression and activity	2	HDAC1, HDAC3
STAT3 nuclear events downstream of ALK signaling	2	HDAC1, HDAC3
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	2	HDAC1, HDAC3
Transcription of E2F targets under negative control by DREAM complex	1	HDAC1
Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1	1	HDAC1
G0 and Early G1	1	HDAC1
PPARA activates gene expression	1	HDAC3
Formation of the beta-catenin:TCF transactivating complex	1	HDAC1
Transcriptional activation of mitochondrial biogenesis	1	HDAC3
Downregulation of SMAD2/3:SMAD4 transcriptional activity	1	HDAC1
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	1	HDAC1
Deactivation of the beta-catenin transactivating complex	1	HDAC1
Transcriptional regulation of white adipocyte differentiation	1	HDAC3
Association of TriC/CCT with target proteins during biosynthesis	1	HDAC3
Regulation of lipid metabolism by PPARalpha	1	HDAC3
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	1	HDAC1
NoRC negatively regulates rRNA expression	1	HDAC1
SUMOylation of chromatin organization proteins	1	HDAC1
Repression of WNT target genes	1	HDAC1
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	HDAC3
Regulation of TP53 Activity through Acetylation	1	HDAC1
G1/S-Specific Transcription	1	HDAC1
RNA Polymerase I Transcription Initiation	1	HDAC1

Dominant GO biological processes

GO term	Targets
negative regulation of transcription by RNA polymerase II	2
chromatin organization	2
protein deacetylation	2
circadian regulation of gene expression	2
negative regulation of apoptotic process	2
negative regulation of DNA-templated transcription	2
positive regulation of transcription by RNA polymerase II	2
rhythmic process	2
establishment of mitotic spindle orientation	1
in utero embryonic development	1
positive regulation of protein phosphorylation	1
transcription by RNA polymerase II	1
regulation of mitotic cell cycle	1
response to xenobiotic stimulus	1
positive regulation of protein ubiquitination	1

Indications & clinical

Indications

7 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
renal cell carcinoma	3	MONDO:0005086	EFO:0000681
diffuse large B-cell lymphoma	2	MONDO:0018905	EFO:0000403
follicular lymphoma	2	MONDO:0018906	MONDO:0018906
Hodgkins lymphoma	1	MONDO:0004952	EFO:0000183
neoplasm	1	MONDO:0005070	EFO:0000616
sarcoma	1	MONDO:0005089	EFO:0000691
non-Hodgkin lymphoma	1	MONDO:0018908	EFO:0005952

Clinical trials

Total trials: 14.

Phase distribution

Phase	Trials
PHASE1	7
PHASE1/PHASE2	3
PHASE2	3
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03592472	PHASE3	RECRUITING	A Study of Pazopanib With or Without Abexinostat in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma (RENAVIV)
NCT03600441	PHASE2	ACTIVE_NOT_RECRUITING	Study of Abexinostat in Patients With Relapsed or Refractory Follicular Lymphoma
NCT03934567	PHASE2	ACTIVE_NOT_RECRUITING	A Multi-Center Phase 2 Study to Evaluate Efficacy and Safety of Oral Abexinostat as Monotherapy in Patients With Relapsed or Refractory Follicular Lymphoma
NCT03936153	PHASE2	RECRUITING	Study to Evaluate Efficacy and Safety of Oral Abexinostat in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)
NCT04024696	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Clinical Study to Evaluate Pharmacokinetics, Safety, and Tolerability of Abexinostat in Chinese Patients
NCT00724984	PHASE1/PHASE2	COMPLETED	Study of the Safety and Tolerability of PCI-24781 in Patients With Lymphoma
NCT01027910	PHASE1/PHASE2	COMPLETED	PCI-24781 in Combination With Doxorubicin to Treat Sarcoma
NCT05698524	PHASE1	RECRUITING	A Study of Temodar With Abexinostat (PCI-24781) for Patients With Recurrent Glioma
NCT00562224	PHASE1	COMPLETED	Study of the Safety and Tolerability of Oral Capsule Form of PCI-24781 in Advanced Cancer Patients
NCT01149668	PHASE1	COMPLETED	A Safety and Tolerability Study of PCI-24781 in Subjects With Cancer
NCT01543763	PHASE1	COMPLETED	Pazopanib in Combination With PCI-24781 in Patients With Metastatic Solid Tumors
NCT03590054	PHASE1	COMPLETED	Abexinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumor Malignancies
NCT03939182	PHASE1	COMPLETED	Abexinostat and Ibrutinib in Diffuse Large B-cell Lymphoma and Mantle Cell Lymphoma
NCT04498520	PHASE1	WITHDRAWN	Abexinostat, Palbociclib, and Fulvestrant for the Treatment of Breast or Gynecologic Cancer

Clinical evidence (CIViC)

Variant × indication × effect (1 predictive associations from 1 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
HDAC2 Expression	Renal Cell Carcinoma	Sensitivity/Response	Pazopanib + Abexinostat	CIViC B	EID7057

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

42 molecules share ≥1 primary target. Top 42 by shared-target count:

Molecule	Source	Status	Shared targets
BELINOSTAT	ChEMBL	Phase 4 (approved)	HDAC1, HDAC3
BENDAMUSTINE	ChEMBL	Phase 4 (approved)	HDAC1, HDAC3
BORTEZOMIB	ChEMBL	Phase 4 (approved)	HDAC1, HDAC3
CELECOXIB	ChEMBL	Phase 4 (approved)	HDAC1, HDAC3
GIVINOSTAT	ChEMBL	Phase 4 (approved)	HDAC1, HDAC3
PANOBINOSTAT	ChEMBL	Phase 4 (approved)	HDAC1, HDAC3
PHENYLBUTANOIC ACID	ChEMBL	Phase 4 (approved)	HDAC1, HDAC3
ROMIDEPSIN	ChEMBL	Phase 4 (approved)	HDAC1, HDAC3
SODIUM PHENYLBUTYRATE	ChEMBL	Phase 4 (approved)	HDAC1, HDAC3
VORINOSTAT	ChEMBL	Phase 4 (approved)	HDAC1, HDAC3
CAFFEIC ACID	ChEMBL	Phase 3	HDAC1, HDAC3
CURCUMIN	ChEMBL	Phase 3	HDAC1, HDAC3
ENTINOSTAT	ChEMBL	Phase 3	HDAC1, HDAC3
PRACINOSTAT	ChEMBL	Phase 3	HDAC1, HDAC3
TACEDINALINE	ChEMBL	Phase 3	HDAC1, HDAC3
TUCIDINOSTAT	ChEMBL	Phase 3	HDAC1, HDAC3
AR-42	ChEMBL	Phase 2	HDAC1, HDAC3
BUTYRIC ACID	ChEMBL	Phase 2	HDAC1, HDAC3
CHLOROGENIC ACID	ChEMBL	Phase 2	HDAC1, HDAC3
CITARINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC3
DACINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC3
DOMATINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC3
FIMEPINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC3
MOCETINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC3
NANATINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC3
QUISINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC3
RICOLINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC3
SODIUM BUTYRATE	ChEMBL	Phase 2	HDAC1, HDAC3
TINOSTAMUSTINE	ChEMBL	Phase 2	HDAC1, HDAC3
Pazopanib	PubChem	Approved	HDAC1, HDAC3
ATORVASTATIN	ChEMBL	Phase 4 (approved)	HDAC1
DAUNORUBICIN	ChEMBL	Phase 4 (approved)	HDAC1
EXIFONE	ChEMBL	Phase 4 (approved)	HDAC1
LOVASTATIN	ChEMBL	Phase 4 (approved)	HDAC1
MOMELOTINIB	ChEMBL	Phase 4 (approved)	HDAC1
VALPROIC ACID	ChEMBL	Phase 4 (approved)	HDAC1
BAICALEIN	ChEMBL	Phase 2	HDAC1
MOLIBRESIB	ChEMBL	Phase 2	HDAC1
NICOXAMAT	ChEMBL	Phase 2	HDAC1
RESMINOSTAT	ChEMBL	Phase 2	HDAC1
Crizotinib	PubChem	Approved	HDAC1
Idelalisib	PubChem	Approved	HDAC1