Methyldopa

Summary

Methyldopa (CHEMBL459) is an approved small-molecule antihypertensive agent (ATC C02AB01) targeting DDC; indicated across 3 conditions including hypertensive disorder and preeclampsia.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C02AB01
• Targets: 1 (DDC)
• Indications: 3 conditions
• Clinical trials: 12
• Chemistry: 211.21 Da · C10H13NO4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL459
Name	Methyldopa
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	38853
ChEBI	CHEBI:61058
ATC	C02AB01
Molecular formula	C10H13NO4
Molecular weight	211.21
InChIKey	CJCSPKMFHVPWAR-JTQLQIEISA-N

SMILES: C[C@](CC1=CC(=C(C=C1)O)O)(C(=O)O)N

IUPAC name: (2S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid

ChEBI definition: A derivative of L-tyrosine having a methyl group at the α-position and an additional hydroxy group at the 3-position on the phenyl ring.

Pharmacological roles (ChEBI): hapten, antihypertensive agent, α-adrenergic agonist, peripheral nervous system drug, sympatholytic agent.

Also known as: (-)-.alpha.-methyldopa, (s)-(-)-.alpha.-methyldopa, Aldomet, Alpha-methyldopa, Anhydrous methyldopa, BAYER-1440L, Dopamet, Dopegyt, J9.247I, L-.alpha.-methyldopa, Lederdopa, Medomet

Parent form; salt/anhydrous children: CHEMBL1591707, CHEMBL4063475

Patent coverage: 6,150 distinct patent families (22,004 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 21,852 (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

Broader ChEMBL bioactivity targets: 31 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, Microtubule-associated protein tau, Lysine-specific demethylase 4E, Ubiquitin carboxyl-terminal hydrolase 2, Nuclear receptor ROR-gamma, Fructose-bisphosphate aldolase, ATP-dependent DNA helicase Q1, RecQ-like DNA helicase BLM, 4’-phosphopantetheinyl transferase ffp, 15-hydroxyprostaglandin dehydrogenase [NAD(+)].

Bioactivity

ChEMBL activities: 29 potent at pChembl ≥ 5 of 59 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HSD17B10	6.9	Potency	125.9	nM	CHEMBL_ACT_4821208
TDP1	6.3	Potency	501.2	nM	CHEMBL_ACT_3926684
Q27686	6.1	Potency	794.3	nM	CHEMBL_ACT_3692432
Q27686	6.1	Potency	794.3	nM	CHEMBL_ACT_3701060
TDP1	6.1	Potency	794.3	nM	CHEMBL_ACT_3930706
POLB	5.95	Potency	1122	nM	CHEMBL_ACT_5027065
ALOX15	5.9	Potency	1259	nM	CHEMBL_ACT_4444010
RECQL	5.85	Potency	1412	nM	CHEMBL_ACT_5052259
POLB	5.85	Potency	1412	nM	CHEMBL_ACT_5075254
PTGS2	5.72	AC50	1900	nM	CHEMBL_ACT_25166651
P12530	5.67	IC50	2126	nM	CHEMBL_ACT_7764619
RECQL	5.65	Potency	2239	nM	CHEMBL_ACT_3694400
KDM4E	5.52	IC50	3000	nM	CHEMBL_ACT_14927425
MAPT	5.5	Potency	3162	nM	CHEMBL_ACT_3967869
MAPT	5.5	Potency	3162	nM	CHEMBL_ACT_4040423
RECQL	5.45	Potency	3548	nM	CHEMBL_ACT_3673589
BLM	5.45	Potency	3548	nM	CHEMBL_ACT_4749955
GAA	5.45	Potency	3548	nM	CHEMBL_ACT_4902256
BLM	5.45	Potency	3548	nM	CHEMBL_ACT_4937754
KDM4E	5.4	Potency	3981	nM	CHEMBL_ACT_3710158
FYN	5.29	IC50	5176	nM	CHEMBL_ACT_7766696
EGFR	5.28	IC50	5228	nM	CHEMBL_ACT_7766694
ALDH1A1	5.25	Potency	5623	nM	CHEMBL_ACT_4140903
MAPT	5.25	Potency	5623	nM	CHEMBL_ACT_4507548
ADRA1A	5.15	AC50	7100	nM	CHEMBL_ACT_25138196
MAPT	5.15	Potency	7080	nM	CHEMBL_ACT_3966163
MAPT	5.15	Potency	7080	nM	CHEMBL_ACT_4027603
MAPT	5.15	Potency	7080	nM	CHEMBL_ACT_4513898
APEX1	5.1	Potency	7943	nM	CHEMBL_ACT_4715446

Target pathways

Aggregated over 1 target gene(s): DDC.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Catecholamine biosynthesis	1	DDC
Serotonin and melatonin biosynthesis	1	DDC

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

Indications & clinical

Indications

3 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
hypertensive disorder	4	MONDO:0005044	EFO:0000537
preeclampsia	2	MONDO:0005081	EFO:0000668
type 1 diabetes mellitus	2	MONDO:0005147	MONDO:0005147

Clinical trials

Total trials: 12.

Phase distribution

Phase	Trials
PHASE4	4
Not specified	3
PHASE2	2
PHASE1	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00117546	PHASE4	UNKNOWN	Cardiovascular and Autonomic Reactivity in Women With a History of Pre-eclampsia
NCT01912677	PHASE4	COMPLETED	Oral Antihypertensive Regimens for Management of Hypertension in Pregnancy
NCT02531490	PHASE4	UNKNOWN	Early Vascular Adjustments During Hypertensive Pregnancy
NCT04835233	PHASE4	COMPLETED	Management of Hypertension in the Early Postpartum: a Randomized Controlled Trial
NCT00194974	PHASE1/PHASE2	WITHDRAWN	Treatment Targets for Chronic Hypertension in Pregnancy
NCT01674127	PHASE2	COMPLETED	Effect of Methyldopa on Uterine Artery Diameter in Pregnant Women With Mild Preeclampsia
NCT03396484	PHASE2	WITHDRAWN	Methyldopa for Reduction of DQ8 Antigen Presentation in At-Risk Subjects for Type 1 Diabetes
NCT00580619	PHASE1	COMPLETED	Autonomic Nervous System and Chronic Fatigue Syndrome
NCT00748059	PHASE1	COMPLETED	The Pathophysiology of Orthostatic Hypotension
NCT01883804	Not specified	COMPLETED	Effect of Methyldopa on MHC Class II Antigen Presentation in Type 1 Diabetes
NCT01911494	Not specified	COMPLETED	Community Level Interventions for Pre-eclampsia
NCT05888896	Not specified	UNKNOWN	Effect of Foot Reflexology on Preeclampsia

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

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).