Entacapone

Summary

Entacapone (CHEMBL953) is an approved small-molecule EC 2.1.1.6 (catechol O-methyltransferase) inhibitor (ATC N04BX02) targeting COMT, MPC2, and MPC1L; indicated across 7 conditions including parkinson disease and cocaine dependence.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N04BX02
• Targets: 3 (COMT, MPC2, MPC1L)
• Indications: 7 conditions
• Clinical trials: 28
• Chemistry: 305.29 Da · C14H15N3O5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL953
Name	Entacapone
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5281081
ChEBI	CHEBI:4798
ATC	N04BX02
Molecular formula	C14H15N3O5
Molecular weight	305.29
InChIKey	JRURYQJSLYLRLN-BJMVGYQFSA-N

SMILES: CCN(CC)C(=O)/C(=C/C1=CC(=C(C(=C1)O)O)[N+](=O)[O-])/C#N

IUPAC name: (E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylprop-2-enamide

ChEBI definition: A monocarboxylic acid amide that is N,N-diethylprop-2-enamide in which the hydrogen at position 2 is substituted by a cyano group and the hydrogen at the 3E position is substituted by a 3,4-dihydroxy-5-nitrophenyl group.

Pharmacological roles (ChEBI): EC 2.1.1.6 (catechol O-methyltransferase) inhibitor, antiparkinson drug, central nervous system drug, antidyskinesia agent.

Also known as: Comtan, Comtess, Entacapona, Entacapone, Entacapone component of corbilta, Entacapone component of stalevo, Entacapone orion, Entacapone teva, OR-611, SID26757974, entacapone, ENTACAPONE

Patent coverage: 3,900 distinct patent families (16,791 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 16,662 (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
COMT	Catechol-O-methyltransferase	Inhibition	8.7	2.1%	P21964
MPC2	mitochondrial pyruvate carrier 2	Inhibition	6.22	1%	O95563
MPC1L	mitochondrial pyruvate carrier 1 like	Inhibition	6.2	0%	P0DKB6

Broader ChEMBL bioactivity targets: 12 (assay-derived). Sample: Prelamin-A/C, 4’-phosphopantetheinyl transferase ffp, G-protein coupled receptor 35, Histone-lysine N-methyltransferase 2A, ATP-binding cassette sub-family C member 4, Catechol O-methyltransferase, Menin/Histone-lysine N-methyltransferase MLL, Alpha-ketoglutarate-dependent dioxygenase FTO, Catechol O-methyltransferase, Cytochrome P450 2C9.

Bioactivity

ChEMBL activities: 17 potent at pChembl ≥ 5 of 24 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P22734	8.52	IC50	3.02	nM	CHEMBL_ACT_19443220
P22734	8.46	IC50	3.47	nM	CHEMBL_ACT_19443155
P22734	7.89	IC50	12.8	nM	CHEMBL_ACT_537974
P22734	7.46	IC50	34.45	nM	CHEMBL_ACT_19443171
LMNA	7.35	Potency	44.7	nM	CHEMBL_ACT_3643580
COMT	7.22	IC50	60	nM	CHEMBL_ACT_19330656
P22734	6.64	IC50	230	nM	CHEMBL_ACT_20670529
COMT	6.41	IC50	386	nM	CHEMBL_ACT_16622760
P22734	5.63	IC50	2320	nM	CHEMBL_ACT_1653730
FTO	5.52	IC50	3000	nM	CHEMBL_ACT_19330646
FTO	5.46	IC50	3500	nM	CHEMBL_ACT_24989185
FTO	5.46	IC50	3500	nM	CHEMBL_ACT_26037654
FTO	5.46	IC50	3500	nM	CHEMBL_ACT_29181992
FTO	5.46	IC50	3500	nM	CHEMBL_ACT_29277830
CYP2C9	5.4	IC50	4000	nM	CHEMBL_ACT_29182023
GPR35	5.25	EC50	5660	nM	CHEMBL_ACT_14927323
ABCC4	5.17	IC50	6800	nM	CHEMBL_ACT_18130808

Target pathways

Aggregated over 3 target gene(s): COMT, MPC2, MPC1L.

Top Reactome pathways

7 total, by targets touching each:

Pathway	Targets	Genes
Aerobic respiration and respiratory electron transport	2	MPC1L, MPC2
Metabolism	2	MPC1L, MPC2
Pyruvate metabolism	2	MPC1L, MPC2
Methylation	1	COMT
Enzymatic degradation of dopamine by COMT	1	COMT
Enzymatic degradation of Dopamine by monoamine oxidase	1	COMT
Potential therapeutics for SARS	1	COMT

Dominant GO biological processes

GO term	Targets
pyruvate import into mitochondria	2
behavioral fear response	1
response to hypoxia	1
synaptic transmission, dopaminergic	1
startle response	1
response to amphetamine	1
renin secretion into blood stream	1
glycogen metabolic process	1
prostaglandin metabolic process	1
response to oxidative stress	1
memory	1
visual learning	1
response to xenobiotic stimulus	1
response to wounding	1
response to toxic substance	1

Indications & clinical

Indications

7 indications (1 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
Parkinson disease	4	MONDO:0005180	MONDO:0005180
cocaine dependence	2	MONDO:0005186	EFO:0002610
epilepsy	1	MONDO:0005027	EFO:0000474
obesity disorder	1	MONDO:0011122	EFO:0001073
methamphetamine dependence	0	MONDO:0005419	EFO:0004701
gastrointestinal stromal tumor	0	MONDO:0011719	MONDO:0011719

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 28.

Phase distribution

Phase	Trials
PHASE4	8
PHASE1	7
PHASE1/PHASE2	4
PHASE3	3
PHASE2	3
EARLY_PHASE1	2
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00143026	PHASE4	COMPLETED	Study to Compare the Effect of Treatment With Carbidopa/Levodopa/Entacapone on the Quality of Life of Patients With Parkinson’s Disease. This Study is Not Recruiting in the United States
NCT00219284	PHASE4	COMPLETED	Effects of Carbidopa/Levodopa/Entacapone on Motor Function and Quality of Life in Patients With Parkinson’s Disease
NCT00373087	PHASE4	COMPLETED	COMT Polymorphism and Entacapone Efficacy
NCT00391898	PHASE4	COMPLETED	Efficacy of Levodopa/Carbidopa/Entacapone vs Levodopa/Carbidopa in Parkinson’s Disease Patients With Early Wearing-off
NCT00601978	PHASE4	WITHDRAWN	Carbidopa/Levodopa Versus Carbidopa/Levodopa/Entacapone on Markers of Event Related Potentials (ERPs) in Patients With Idiopathic Parkinson’s Disease (PD) and End-of-dose Wearing Off
NCT00642356	PHASE4	TERMINATED	Carbidopa/Levodopa/Entacapone Versus Immediate Release (IR) Carbidopa/Levodopa on Non-motor Symptoms in Patients With Idiopathic Parkinson’s Disease and Demonstrating Non-motor Symptoms of Wearing Off
NCT00906828	PHASE4	COMPLETED	Pharmacokinetics of Levodopa/Carbidopa Infusion With and Without Oral Catechol-O-methyl Transferase (COMT) Inhibitors
NCT06236230	PHASE4	UNKNOWN	Basic and Clinical Studies of Levodopa/Carbidopa/Entacapone in the Treatment of Early Parkinson’s Disease
NCT00099268	PHASE3	COMPLETED	Efficacy and Safety of Carbidopa/Levodopa/Entacapone in Patients With Parkinson’s Disease Requiring Initiation of Levodopa Therapy
NCT00134966	PHASE3	COMPLETED	A Study to Evaluate Fixed Dose Carbidopa/Levodopa/Entacapone Versus Immediate Release Carbidopa/Levodopa
NCT01568073	PHASE3	COMPLETED	Efficacy and Safety of BIA 9-1067 in Idiopathic Parkinson’s Disease Patients With Wearing-off Phenomenon
NCT00262470	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Treatment of Orthostatic Intolerance
NCT00200447	PHASE2	COMPLETED	An Open-Label Feasibility/Pilot Study With [123I]-IBZM SPECT (DOPA-SYN)
NCT00237263	PHASE2	COMPLETED	An Extension Study of Entacapone in Patients With Parkinson’s Disease With End-of-dose Wearing-off. This Study is Not Recruiting in the United States
NCT00491998	PHASE1/PHASE2	COMPLETED	PK, PD and Safety of Multiple Doses of V1512 Tablets in PD Patients Compared to Standard Levodopa/Carbidopa Oral Tablets
NCT00547911	PHASE1/PHASE2	TERMINATED	Augmenting Effects of L-DOPS With Carbidopa and Entacapone
NCT00562198	PHASE2	TERMINATED	PET-Study: Effects of Single Doses of Stalevo and Levodopa/Carbidopa on Striatal 11C-Raclopride Binding
NCT02349243	PHASE1/PHASE2	UNKNOWN	Effect of Entacapone on Bodyweight Loss in Obese Population
NCT00693862	PHASE1	COMPLETED	Pharmacokinetic Study With Repeated Doses of Stalevo
NCT01519284	PHASE1	COMPLETED	Study of BIA 9-1067 to Investigate Its Effect on Levodopa Pharmacokinetic
NCT01688089	PHASE1	COMPLETED	Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ODM-103 in Healthy Volunteers
NCT01840423	PHASE1	COMPLETED	Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ODM-104 in Healthy Volunteers
NCT02096601	PHASE1	COMPLETED	A Safety, Tolerability, and Pharmacokinetic Study of ND0612 Delivered as a Continuous Subcutaneous in Parkinson’s Disease Patients
NCT02170376	PHASE1	COMPLETED	The Effect of BIA 9-1067 at Steady-state on the Levodopa Pharmacokinetics
NCT02554734	PHASE1	COMPLETED	Pharmacokinetic Study in Healthy Volunteers
NCT02058966	EARLY_PHASE1	COMPLETED	Pilot Study of Entacapone for Methamphetamine Abuse
NCT04006769	EARLY_PHASE1	COMPLETED	Entacapone Combination With Imatinib for Treatment of GIST
NCT00192855	Not specified	COMPLETED	Entacapone Augmentation for Schizophrenia

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 3 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

16 molecules share ≥1 primary target. Top 16 by shared-target count:

Molecule	Source	Status	Shared targets
OPICAPONE	ChEMBL	Phase 4 (approved)	COMT
TOLCAPONE	ChEMBL	Phase 4 (approved)	COMT
MITOGLITAZONE	ChEMBL	Phase 2	MPC2
Afatinib	PubChem	Approved	COMT
alfaxalone	PubChem	Approved	COMT
Apixaban	PubChem	Approved	COMT
Binimetinib	PubChem	Approved	COMT
Diacetyl benzoyl lathyrol	PubChem	Approved	COMT
Edoxaban	PubChem	Approved	COMT
Fulvestrant	PubChem	Approved	COMT
Imipenem	PubChem	Approved	COMT
Linagliptin	PubChem	Approved	COMT
Pazopanib	PubChem	Approved	COMT
Pimavanserin	PubChem	Approved	COMT
Pyrazinamide	PubChem	Approved	COMT
Selumetinib	PubChem	Approved	COMT