Tacedinaline

Summary

Tacedinaline (CHEMBL235191) is a phase-3 clinical-stage small-molecule EC 3.5.1.98 (histone deacetylase) inhibitor targeting HDAC2, HDAC3, and HDAC1; indicated across 3 conditions including lung neoplasm and plasma cell myeloma.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 3 (HDAC2, HDAC3, HDAC1)
• Indications: 3 conditions
• Clinical trials: 3
• Chemistry: 269.3 Da · C15H15N3O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL235191
Name	Tacedinaline
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	2746
ChEBI	CHEBI:90195
Molecular formula	C15H15N3O2
Molecular weight	269.3
InChIKey	VAZAPHZUAVEOMC-UHFFFAOYSA-N

SMILES: CC(=O)NC1=CC=C(C=C1)C(=O)NC2=CC=CC=C2N

IUPAC name: 4-acetamido-N-(2-aminophenyl)benzamide

ChEBI definition: A benzamide obtained by formal condensation of the carboxy group of 4-acetamidobenzoic acid with one of the amino groups of 1,2-phenylenediamine. An oral cytostatic drug with impressive differential activity against leukemic cells and normal stem-cells. Also used in combination therapy for selected tumors including non-smoll cell lung, pancreatic, breast, and colorectal cancers.

Pharmacological roles (ChEBI): EC 3.5.1.98 (histone deacetylase) inhibitor, antineoplastic agent.

Also known as: Acetyldinaline, CI-994, GOE 5549, GOE-5549, PD 123654, PD-123654, Tacedinalina, Tacedinaline, TACEDINALINE, CI994 (TACEDINALINE), CI994 (Tacedinaline), Tacedinalin

Patent coverage: 1,003 distinct patent families (2,950 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 2,830 (96%) 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
HDAC2	histone deacetylase 2	Inhibition	6.82	3.1%	Q92769
HDAC3	histone deacetylase 3	Inhibition	6.26	95.1% (common-essential)	O15379
HDAC1	histone deacetylase 1	Inhibition	6.24	4.5%	Q13547

Broader ChEMBL bioactivity targets: 8 (assay-derived). Sample: Bromodomain-containing protein 4, Histone deacetylase 3, Histone deacetylase 2, Histone deacetylase, Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2), Histone deacetylase 1, Histone deacetylase 11, Polyamine deacetylase HDAC10.

Bioactivity

ChEMBL activities: 48 potent at pChembl ≥ 5 of 49 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HDAC1	7.41	IC50	39	nM	CHEMBL_ACT_28736063
HDAC1	7.41	IC50	39	nM	CHEMBL_ACT_28736102
HDAC1	7.39	IC50	41	nM	CHEMBL_ACT_19249733
HDAC1	7.39	IC50	41	nM	CHEMBL_ACT_28575992
HDAC3	7.34	IC50	46	nM	CHEMBL_ACT_19249729
HDAC3	7.34	IC50	46	nM	CHEMBL_ACT_28576040
HDAC1	7.3	Ki	50	nM	CHEMBL_ACT_3389927
HDAC1	7.22	IC50	60	nM	CHEMBL_ACT_18091006
BRD4	7.13	IC50	74	nM	CHEMBL_ACT_25031518
HDAC3	6.98	Ki	105	nM	CHEMBL_ACT_25472506
HDAC3	6.97	IC50	106.2	nM	CHEMBL_ACT_26197166
HDAC1	6.89	IC50	130	nM	CHEMBL_ACT_22799474
HDAC2	6.83	IC50	147	nM	CHEMBL_ACT_19249731
HDAC2	6.83	IC50	147	nM	CHEMBL_ACT_28576016
HDAC3	6.72	IC50	190	nM	CHEMBL_ACT_22799490
HDAC2	6.72	Ki	190	nM	CHEMBL_ACT_3389928
HDAC2	6.44	IC50	363.9	nM	CHEMBL_ACT_26197145
HDAC1	6.4	IC50	394.2	nM	CHEMBL_ACT_26197124
HDAC3	6.26	Ki	550	nM	CHEMBL_ACT_3389929
HDAC1	6.24	IC50	570	nM	CHEMBL_ACT_2099187
BRD4	6.14	IC50	729	nM	CHEMBL_ACT_25031493
HDAC2	6.08	IC50	830	nM	CHEMBL_ACT_22799482
HDAC1	6.05	IC50	900	nM	CHEMBL_ACT_1998281
HDAC2	6.05	IC50	900	nM	CHEMBL_ACT_1998288
HDAC1	6.02	IC50	960	nM	CHEMBL_ACT_25031484
HDAC1	6.02	IC50	960	nM	CHEMBL_ACT_26153227
HDAC1	5.96	IC50	1090	nM	CHEMBL_ACT_18439309
HDAC1	5.92	IC50	1200	nM	CHEMBL_ACT_18090857
HDAC2	5.92	IC50	1200	nM	CHEMBL_ACT_18094896
HDAC2	5.92	IC50	1200	nM	CHEMBL_ACT_18689933

Target pathways

Aggregated over 3 target gene(s): HDAC2, HDAC3, HDAC1.

Top Reactome pathways

58 total, by targets touching each:

Pathway	Targets	Genes
p75NTR negatively regulates cell cycle via SC1	3	HDAC1, HDAC2, HDAC3
NOTCH1 Intracellular Domain Regulates Transcription	3	HDAC1, HDAC2, HDAC3
Constitutive Signaling by NOTCH1 PEST Domain Mutants	3	HDAC1, HDAC2, HDAC3
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	3	HDAC1, HDAC2, HDAC3
HDACs deacetylate histones	3	HDAC1, HDAC2, HDAC3
Notch-HLH transcription pathway	3	HDAC1, HDAC2, HDAC3
Regulation of PTEN gene transcription	3	HDAC1, HDAC2, HDAC3
Regulation of MECP2 expression and activity	3	HDAC1, HDAC2, HDAC3
STAT3 nuclear events downstream of ALK signaling	3	HDAC1, HDAC2, HDAC3
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	3	HDAC1, HDAC2, HDAC3
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	2	HDAC1, HDAC2
NoRC negatively regulates rRNA expression	2	HDAC1, HDAC2
SUMOylation of chromatin organization proteins	2	HDAC1, HDAC2
Regulation of TP53 Activity through Acetylation	2	HDAC1, HDAC2
RNA Polymerase I Transcription Initiation	2	HDAC1, HDAC2
MECP2 regulates neuronal receptors and channels	2	HDAC1, HDAC2
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	2	HDAC1, HDAC2
Potential therapeutics for SARS	2	HDAC1, HDAC2
Negative Regulation of CDH1 Gene Transcription	2	HDAC1, HDAC2
Factors involved in megakaryocyte development and platelet production	2	HDAC1, HDAC2
Regulation of endogenous retroelements by KRAB-ZFP proteins	2	HDAC1, HDAC2
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	2	HDAC1, HDAC2
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	2	HDAC1, HDAC2
NuRD complex assembly	2	HDAC1, HDAC2
Interaction of NuRD complexes with transcription factors	2	HDAC1, HDAC2
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

Dominant GO biological processes

GO term	Targets
negative regulation of transcription by RNA polymerase II	3
circadian regulation of gene expression	3
negative regulation of apoptotic process	3
negative regulation of DNA-templated transcription	3
positive regulation of transcription by RNA polymerase II	3
chromatin organization	3
rhythmic process	3
chromatin remodeling	2
positive regulation of cell population proliferation	2
response to xenobiotic stimulus	2
epidermal cell differentiation	2
negative regulation of cell migration	2
negative regulation of transforming growth factor beta receptor signaling pathway	2
heterochromatin formation	2
positive regulation of intracellular estrogen receptor signaling pathway	2

Indications & clinical

Indications

3 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
lung neoplasm	3	MONDO:0021117	MONDO:0008903
plasma cell myeloma	2	MONDO:0009693	EFO:0001378
exocrine pancreatic carcinoma	2	MONDO:0005192	EFO:0002618

Clinical trials

Total trials: 3.

Phase distribution

Phase	Trials
PHASE2	2
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00005093	PHASE3	COMPLETED	Gemcitabine With or Without CI-994 in Treating Patients With Advanced Non-small Cell Lung Cancer
NCT00004861	PHASE2	COMPLETED	Gemcitabine With or Without CI-994 in Treating Patients With Advanced Pancreatic Cancer
NCT00005624	PHASE2	COMPLETED	CI-994 in Treating Patients With Advanced Myeloma

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

43 molecules share ≥1 primary target. Top 43 by shared-target count:

Molecule	Source	Status	Shared targets
BELINOSTAT	ChEMBL	Phase 4 (approved)	HDAC1, HDAC2, HDAC3
BENDAMUSTINE	ChEMBL	Phase 4 (approved)	HDAC1, HDAC2, HDAC3
BORTEZOMIB	ChEMBL	Phase 4 (approved)	HDAC1, HDAC2, HDAC3
CELECOXIB	ChEMBL	Phase 4 (approved)	HDAC1, HDAC2, HDAC3
GIVINOSTAT	ChEMBL	Phase 4 (approved)	HDAC1, HDAC2, HDAC3
PANOBINOSTAT	ChEMBL	Phase 4 (approved)	HDAC1, HDAC2, HDAC3
PHENYLBUTANOIC ACID	ChEMBL	Phase 4 (approved)	HDAC1, HDAC2, HDAC3
ROMIDEPSIN	ChEMBL	Phase 4 (approved)	HDAC1, HDAC2, HDAC3
SODIUM PHENYLBUTYRATE	ChEMBL	Phase 4 (approved)	HDAC1, HDAC2, HDAC3
VORINOSTAT	ChEMBL	Phase 4 (approved)	HDAC1, HDAC2, HDAC3
ABEXINOSTAT	ChEMBL	Phase 3	HDAC1, HDAC2, HDAC3
CAFFEIC ACID	ChEMBL	Phase 3	HDAC1, HDAC2, HDAC3
CURCUMIN	ChEMBL	Phase 3	HDAC1, HDAC2, HDAC3
ENTINOSTAT	ChEMBL	Phase 3	HDAC1, HDAC2, HDAC3
PRACINOSTAT	ChEMBL	Phase 3	HDAC1, HDAC2, HDAC3
TUCIDINOSTAT	ChEMBL	Phase 3	HDAC1, HDAC2, HDAC3
AR-42	ChEMBL	Phase 2	HDAC1, HDAC2, HDAC3
BUTYRIC ACID	ChEMBL	Phase 2	HDAC1, HDAC2, HDAC3
CHLOROGENIC ACID	ChEMBL	Phase 2	HDAC1, HDAC2, HDAC3
CITARINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC2, HDAC3
DACINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC2, HDAC3
DOMATINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC2, HDAC3
FIMEPINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC2, HDAC3
MOCETINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC2, HDAC3
NANATINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC2, HDAC3
QUISINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC2, HDAC3
RICOLINOSTAT	ChEMBL	Phase 2	HDAC1, HDAC2, HDAC3
SODIUM BUTYRATE	ChEMBL	Phase 2	HDAC1, HDAC2, HDAC3
TINOSTAMUSTINE	ChEMBL	Phase 2	HDAC1, HDAC2, HDAC3
Pazopanib	PubChem	Approved	HDAC1, HDAC2, HDAC3
ATORVASTATIN	ChEMBL	Phase 4 (approved)	HDAC1, HDAC2
LOVASTATIN	ChEMBL	Phase 4 (approved)	HDAC1, HDAC2
VALPROIC ACID	ChEMBL	Phase 4 (approved)	HDAC1, HDAC2
MOLIBRESIB	ChEMBL	Phase 2	HDAC1, HDAC2
Crizotinib	PubChem	Approved	HDAC1, HDAC2
DAUNORUBICIN	ChEMBL	Phase 4 (approved)	HDAC1
EXIFONE	ChEMBL	Phase 4 (approved)	HDAC1
MOMELOTINIB	ChEMBL	Phase 4 (approved)	HDAC1
EBSELEN	ChEMBL	Phase 3	HDAC2
BAICALEIN	ChEMBL	Phase 2	HDAC1
NICOXAMAT	ChEMBL	Phase 2	HDAC1
RESMINOSTAT	ChEMBL	Phase 2	HDAC1
Idelalisib	PubChem	Approved	HDAC1