Benserazide

Summary

Benserazide (CHEMBL1096979) is a phase-3 clinical-stage small-molecule EC 4.1.1.28 (aromatic-L-amino-acid decarboxylase) inhibitor targeting DDC and CBS; indicated across 2 conditions including restless legs syndrome and parkinson disease.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 2 (DDC, CBS)
• Indications: 2 conditions
• Clinical trials: 6
• Chemistry: 257.24 Da · C10H15N3O5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1096979
Name	Benserazide
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	2327
ChEBI	CHEBI:64187
Molecular formula	C10H15N3O5
Molecular weight	257.24
InChIKey	BNQDCRGUHNALGH-UHFFFAOYSA-N

SMILES: C1=CC(=C(C(=C1CNNC(=O)C(CO)N)O)O)O

IUPAC name: 2-amino-3-hydroxy-N’-[(2,3,4-trihydroxyphenyl)methyl]propanehydrazide

ChEBI definition: A carbohydrazide that results from the formal condensation of the carboxy group of DL-serine with the primary amino group of 4-(hydrazinylmethyl)benzene-1,2,3-triol. An aromatic-L-amino-acid decarboxylase inhibitor (DOPA decarboxylase inhibitor) that does not enter the central nervous system, it is used as its hydrochloride salt as an adjunct to levodopa in the treatment of parkinsonism. By preventing the conversion of levodopa to dopamine in the periphery, it causes an increase in the amount of levodopa reaching the central nervous system and so reduces the required dose. Benserazide has no antiparkinson actions when given alone.

Pharmacological roles (ChEBI): EC 4.1.1.28 (aromatic-L-amino-acid decarboxylase) inhibitor, antiparkinson drug, dopaminergic agent.

Also known as: Benserazida, Benserazide, Benserazide (as hydrochloride), Benserazide component of madopar, Benserazide component of prolopa, Benserazide hcl, Benserazide hydrochloride, NSC-755907, Serazide, benserazide, SID90341370, BENSERAZIDE

Parent form; salt/anhydrous children: CHEMBL1255778

Patent coverage: 2,505 distinct patent families (9,306 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 9,207 (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
DDC	L-Aromatic amino-acid decarboxylase	Inhibition		0.1%	P20711
CBS	Cystathionine β-synthase	Inhibition	4.52	0.4%	P35520

Broader ChEMBL bioactivity targets: 10 (assay-derived). Sample: Estrogen receptor, Prostaglandin G/H synthase 2, Delta-type opioid receptor, Genome polyprotein, Estrogen receptor beta, Adenosine receptor A3, Hexokinase-2, Serine/threonine-protein kinase mTOR, Replicase polyprotein 1ab, Neuropeptide Y receptor type 1.

Bioactivity

ChEMBL activities: 6 potent at pChembl ≥ 5 of 11 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P0DTD1	6.85	IC50	140	nM	CHEMBL_ACT_19964211
PTGS2	6.69	AC50	205	nM	CHEMBL_ACT_25166223
ESR1	5.76	AC50	1720	nM	CHEMBL_ACT_25167335
P03313	5.62	IC50	2400	nM	CHEMBL_ACT_16738419
HK2	5.26	IC50	5520	nM	CHEMBL_ACT_18915047
NPY1R	5.25	AC50	5670	nM	CHEMBL_ACT_25186544

Target pathways

Aggregated over 2 target gene(s): DDC, CBS.

Top Reactome pathways

8 total, by targets touching each:

Pathway	Targets	Genes
Metabolism	1	CBS
Cysteine formation from homocysteine	1	CBS
Sulfur amino acid metabolism	1	CBS
Catecholamine biosynthesis	1	DDC
Serotonin and melatonin biosynthesis	1	DDC
Metabolism of ingested SeMet, Sec, MeSec into H2Se	1	CBS
Selenoamino acid metabolism	1	CBS
Metabolism of amino acids and derivatives	1	CBS

Dominant GO biological processes

GO term	Targets
kidney development	1
amino acid metabolic process	1
catecholamine metabolic process	1
response to toxic substance	1
gene expression	1
carboxylic acid metabolic process	1
dopamine biosynthetic process	1
serotonin biosynthetic process	1
biogenic amine metabolic process	1
biogenic amine biosynthetic process	1
catecholamine biosynthetic process	1
endochondral ossification	1
blood vessel remodeling	1
obsolete L-cysteine biosynthetic process from L-serine	1
L-serine metabolic process	1

Indications & clinical

Indications

2 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
restless legs syndrome	3	MONDO:0005391	EFO:0004270
Parkinson disease	3	MONDO:0005180	MONDO:0005180

Clinical trials

Total trials: 6.

Phase distribution

Phase	Trials
PHASE3	2
PHASE1	2
PHASE4	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01327261	PHASE4	COMPLETED	Fasting Comparative Bioavailability of Two Tablet Formulations of Levodopa /Benserazide in Healthy Volunteers
NCT01227655	PHASE3	COMPLETED	Efficacy and Safety of BIA 9-1067 in Idiopathic Parkinson’s Disease Patients.
NCT01568073	PHASE3	COMPLETED	Efficacy and Safety of BIA 9-1067 in Idiopathic Parkinson’s Disease Patients With Wearing-off Phenomenon
NCT01533116	PHASE1	COMPLETED	Effect of BIA 9-1067 at Steady-state on the Pharmacokinetics of Levodopa/Carbidopa and Levodopa/Benserazide
NCT02169414	PHASE1	COMPLETED	Effect of Three Multiple-dose Regimens of BIA 9 1067 at Steady-state on the Levodopa Pharmacokinetics
NCT00941265	Not specified	COMPLETED	Effect of Dopaminergic Medication on Recovery of Aphasia

Clinical evidence (CIViC)

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

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.

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

Molecule	Source	Status	Shared targets
HYPERICIN	ChEMBL	Phase 3	CBS