Melatonin

Summary

Melatonin (CHEMBL45) is an approved small-molecule hormone (ATC N05CH01) targeting MTNR1A and MTNR1B; indicated across 74 conditions including insomnia and autism.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N05CH01
• Targets: 2 (MTNR1A, MTNR1B)
• Indications: 74 conditions
• Clinical trials: 394
• Chemistry: 232.28 Da · C13H16N2O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL45
Name	Melatonin
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	896
ChEBI	CHEBI:16796
ATC	N05CH01
Molecular formula	C13H16N2O2
Molecular weight	232.28
InChIKey	DRLFMBDRBRZALE-UHFFFAOYSA-N

SMILES: CC(=O)NCCC1=CNC2=C1C=C(C=C2)OC

IUPAC name: N-[2-(5-methoxy-1H-indol-3-yl)ethyl]acetamide

ChEBI definition: A member of the class of acetamides that is acetamide in which one of the hydrogens attached to the nitrogen atom is replaced by a 2-(5-methoxy-1H-indol-3-yl)ethyl group. It is a hormone secreted by the pineal gland in humans.

Pharmacological roles (ChEBI): hormone, anticonvulsant, immunological adjuvant, radical scavenger, central nervous system depressant, geroprotector.

Other ChEBI roles (chemical / environmental): human metabolite, mouse metabolite.

Also known as: BCI-049, Circadin, General nutrit, Health aid, Heidadouppi, Icenia, J5.258B, Life ext, Melapure, Melatol, Melatonin, Melatonin neurim

Patent coverage: 20,395 distinct patent families (56,417 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 55,985 (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
MTNR1A	MT1 receptor	Full agonist	9.9	0%	P48039
MTNR1B	MT2 receptor	Full agonist	9.6	0.2%	P49286

Broader ChEMBL bioactivity targets: 28 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, Lysine-specific demethylase 4E, RecQ-like DNA helicase BLM, 4’-phosphopantetheinyl transferase ffp, 15-hydroxyprostaglandin dehydrogenase [NAD(+)], Ras-related protein Rab-9A, Peripheral myelin protein 22, 5-hydroxytryptamine receptor 2B, Melatonin receptor type 1A, Melatonin receptor type 1B.

Bioactivity

ChEMBL activities: 220 potent at pChembl ≥ 5 of 238 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
MTNR1A	10.77	IC50	0.02	nM	CHEMBL_ACT_264146
MTNR1A	10.66	EC50	0.02	nM	CHEMBL_ACT_23270193
MTNR1A	10.59	EC50	0.03	nM	CHEMBL_ACT_6198899
MTNR1A	10.59	EC50	0.03	nM	CHEMBL_ACT_6275469
MTNR1A	10.2	EC50	0.06	nM	CHEMBL_ACT_25560391
MTNR1B	10.16	EC50	0.07	nM	CHEMBL_ACT_15618423
MTNR1A	10.16	EC50	0.07	nM	CHEMBL_ACT_24827722
MTNR1B	10.15	EC50	0.07	nM	CHEMBL_ACT_23267963
P49219	10.1	EC50	0.08	nM	CHEMBL_ACT_1946781
MTNR1A	10.1	Ki	0.08	nM	CHEMBL_ACT_231418
MTNR1B	10.1	EC50	0.08	nM	CHEMBL_ACT_25560402
MTNR1A	10.08	Ki	0.08	nM	CHEMBL_ACT_1026568
MTNR1A	10.08	Ki	0.08	nM	CHEMBL_ACT_888403
MTNR1A	10.08	Ki	0.08	nM	CHEMBL_ACT_888407
P49219	10.07	EC50	0.09	nM	CHEMBL_ACT_1931978
MTNR1A	10.04	Ki	0.09	nM	CHEMBL_ACT_15618306
MTNR1A	10.04	Ki	0.09	nM	CHEMBL_ACT_15760635
MTNR1A	10.04	Ki	0.09	nM	CHEMBL_ACT_523814
MTNR1A	10.01	EC50	0.1	nM	CHEMBL_ACT_15618386
MTNR1A	9.96	IC50	0.11	nM	CHEMBL_ACT_16501817
MTNR1A	9.96	IC50	0.11	nM	CHEMBL_ACT_16838427
MTNR1A	9.96	EC50	0.11	nM	CHEMBL_ACT_23268085
MTNR1A	9.96	Ki	0.11	nM	CHEMBL_ACT_2381374
MTNR1A	9.92	Ki	0.12	nM	CHEMBL_ACT_1301390
MTNR1A	9.92	Ki	0.12	nM	CHEMBL_ACT_17957835
MTNR1B	9.92	Ki	0.12	nM	CHEMBL_ACT_231419
MTNR1B	9.92	Ki	0.12	nM	CHEMBL_ACT_23267931
MTNR1A	9.92	Ki	0.12	nM	CHEMBL_ACT_340179
P49219	9.91	EC50	0.12	nM	CHEMBL_ACT_19107137
MTNR1B	9.89	Ki	0.13	nM	CHEMBL_ACT_22956895

Target pathways

Aggregated over 2 target gene(s): MTNR1A, MTNR1B.

Top Reactome pathways

6 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	2	MTNR1A, MTNR1B
Signaling by GPCR	2	MTNR1A, MTNR1B
Class A/1 (Rhodopsin-like receptors)	2	MTNR1A, MTNR1B
GPCR downstream signalling	2	MTNR1A, MTNR1B
G alpha (i) signalling events	2	MTNR1A, MTNR1B
GPCR ligand binding	2	MTNR1A, MTNR1B

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	2
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	2
signal transduction	2
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
mating behavior	1
circadian rhythm	1
chemical synaptic transmission	1
negative regulation of receptor guanylyl cyclase signaling pathway	1
glucose homeostasis	1
camera-type eye development	1
negative regulation of neuron apoptotic process	1
negative regulation of vasoconstriction	1
positive regulation of circadian sleep/wake cycle, non-REM sleep	1
negative regulation of insulin secretion	1
regulation of insulin secretion	1

Indications & clinical

Indications

74 indications (2 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
insomnia	4	MONDO:0013600	EFO:0004698
autism	4	MONDO:0005260	EFO:0003758
attention deficit-hyperactivity disorder	3	MONDO:0007743	EFO:0003888
neoplasm	3	MONDO:0005070	EFO:0000616
gastroesophageal reflux disease	3	MONDO:0007186	EFO:0003948
Barrett esophagus	3	MONDO:0013662	EFO:0000280
non-small cell lung carcinoma	3	MONDO:0005233	EFO:0003060
anxiety	3	MONDO:0011918	EFO:0005230
autism spectrum disorder	3	MONDO:0005258	EFO:0003756
dementia	3	MONDO:0001627	HP:0000726
sleep disorder	3	MONDO:0100081	EFO:0008568
delirium	3	MONDO:0045057	EFO:0009267
irritable bowel syndrome	3	MONDO:0005052	EFO:0000555
breast neoplasm	3	MONDO:0021100	MONDO:0007254
oral cavity squamous cell carcinoma	3	MONDO:0004958	EFO:0000199
tooth disorder	3	MONDO:0006999	EFO:1001216
depressive disorder	3	MONDO:0002050	MONDO:0002050
acute kidney injury	3	MONDO:0002492	HP:0001919
migraine disorder	3	MONDO:0005277	MONDO:0005277
stroke disorder	3	MONDO:0005098	EFO:0000712
brain injury	3	MONDO:0043510	MONDO:0043510
uveal melanoma	3	MONDO:0006486	EFO:1000616
ocular cancer	3	MONDO:0002236	MONDO:0002236
aortic aneurysm	2	MONDO:0005160	EFO:0001666
metabolic syndrome X	2	MONDO:0011565	EFO:0000195
atopic eczema	2	MONDO:0004980	EFO:0000274
epilepsy	2	MONDO:0005027	EFO:0000474
ulcerative colitis	2	MONDO:0005101	EFO:0000729
hypertensive disorder	2	MONDO:0005044	EFO:0000537
relapsing-remitting multiple sclerosis	2	MONDO:0005314	EFO:0003929
atrial fibrillation	2	MONDO:0004981	EFO:0000275
melanoma	2	MONDO:0005105	EFO:0000756
ischemia reperfusion injury	2	MONDO:0005203	EFO:0002687
fibromyalgia	2	MONDO:0005546	EFO:0005687
head and neck cancer	2	MONDO:0005627	EFO:0006859
burn	2	MONDO:0043519	EFO:0009516
prediabetes syndrome	2	MONDO:0006920	EFO:1001121
major depressive disorder	2	MONDO:0002009	MONDO:0002009
alcohol-related disorders	2	MONDO:0021698	MONDO:0021698
severe acute respiratory syndrome	2	MONDO:0005091	MONDO:0100096
periodontitis	2	MONDO:0005076	EFO:0000649
acute myocardial infarction	2	MONDO:0004781	EFO:0008583
enuresis	2	MONDO:0024290	MONDO:0024290
injury	2	MONDO:0021178	EFO:0000546
dengue disease	2	MONDO:0005502	EFO:0005547
essential hypertension	2	MONDO:0001134	MONDO:0001134
Parkinson disease	2	MONDO:0005180	MONDO:0005180
actinic keratosis	2	MONDO:0005173	EFO:0002496
bipolar disorder	2	MONDO:0004985	MONDO:0004985
sunburn	1	MONDO:0005326	EFO:0003958
substance withdrawal syndrome	1	MONDO:0005567	EFO:0005800
skin disorder	1	MONDO:0005093	EFO:0000701
metabolic disease	1	MONDO:0005066	EFO:0000589
stomatitis	1	MONDO:0004842	EFO:1001904
perinatal asphyxia	1	MONDO:0006663	EFO:1000824
brain ischemia	1	MONDO:0005299	MONDO:0005299
periodontal disorder	1	MONDO:0002635	MONDO:0002635
necrotizing enterocolitis	1	MONDO:0005313	EFO:0003928
multiple sclerosis	1	MONDO:0005301	MONDO:0005301
diabetes mellitus	0	MONDO:0005015	EFO:0000400
obstructive sleep apnea syndrome	0	MONDO:0007147	EFO:0003918

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

Clinical trials

Total trials: 394.

Phase distribution

Phase	Trials
Not specified	129
PHASE2	81
PHASE3	51
PHASE4	48
PHASE2/PHASE3	24
PHASE1	22
EARLY_PHASE1	20
PHASE1/PHASE2	19

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04831398	PHASE4	ACTIVE_NOT_RECRUITING	The Effects of Acute Melatonin Supplementation on Cardiovascular Responses to Sympathetic Activation
NCT05247125	PHASE4	RECRUITING	The Role of Circadian Factors in Regulation of Neuroplasticity in Ischemic Stroke (Interventional)
NCT07034560	PHASE4	ACTIVE_NOT_RECRUITING	Effectiveness of Oral Melatonin vs Oral Tranexamic Acid in the Treatment and Recurrence of Melasma
NCT07036367	PHASE4	RECRUITING	The Use of Sublingual Melatonin Premedication in Geriatric Cataract Surgery
NCT00749814	PHASE4	UNKNOWN	Sleep Disturbances in Hospitalized Children
NCT00834886	PHASE4	COMPLETED	Randomized Controlled Trial on the Treatment Effects of Melatonin and Light Therapy on Delayed Sleep Phase Syndrome
NCT01033565	PHASE4	TERMINATED	Melatonin CR for the Treatment of Impaired Sleep Maintenance in 4-8 Year Old Children With Autism Spectrum Disorders
NCT01087359	PHASE4	COMPLETED	Antiinflammatoric and Antioxidative Effect of Melatonin in Human Endotoxaemia
NCT01267604	PHASE4	WITHDRAWN	Ovarian Stimulation: Inositol and Melatonin
NCT01370486	PHASE4	WITHDRAWN	Melatonin Versus Placebo in the Lennox-Gastaut Syndrome: Neurophysiological and Neuropsychological Effects
NCT01393574	PHASE4	UNKNOWN	Comparing Treatment With Melatonin to Treatment With Stimulants (Methylphenidate) in Children With Attention Deficit Hyperactivity Disorder and Sleep Difficulties
NCT01431092	PHASE4	COMPLETED	Melatonin Versus Placebo for Benzodiazepine Discontinuation in Patients With Schizophrenia
NCT01540747	PHASE4	COMPLETED	Role of Melatonin Supplementation in Follicular Fluid of in Vitro Fertilization (IVF) Patients With Polycystic Ovarian Syndrome
NCT01695070	PHASE4	COMPLETED	Melatonin to Prevent Brain Injury in Unborn Growth Restricted Babies
NCT01811160	PHASE4	COMPLETED	Metabolic Effects of Melatonin in Patients Treated With Second Generation Antipsychotics
NCT01863277	PHASE4	UNKNOWN	Safety Study of Melatonin in Stroke Patients
NCT02282241	PHASE4	WITHDRAWN	Melatonin for Delirium Prophylaxis
NCT02424071	PHASE4	COMPLETED	The Effect of Premedication With Melatonin on Postoperative Recovery From Bariatric Surgery
NCT02591238	PHASE4	COMPLETED	Melatonin in Smoke-induced Vascular Injury
NCT02639741	PHASE4	COMPLETED	Preoperative Melatonin or Vitamin C Administration on Postoperative Analgesia
NCT02836743	PHASE4	UNKNOWN	Effect of Slow-release Melatonin (Circadin®) Therapy on Idiopathic RBD: a Pilot Study
NCT02903901	PHASE4	WITHDRAWN	Melatonin for Prevention of Post- Operative Delirium Pilot Study Protocol
NCT02962037	PHASE4	UNKNOWN	Are Patients Suffering From DSPS Show Compromising in Everyday Functions and Abilities Before Handling the Disorder?
NCT03013790	PHASE4	UNKNOWN	Melatonin Use in the Intensive Care Elderly Population
NCT03066518	PHASE4	COMPLETED	Effect of Melatonin on Sleep Quality in Patients Dementia
NCT03115034	PHASE4	COMPLETED	Melatonin in Patients Under Carotid Endarterectomy
NCT03121521	PHASE4	COMPLETED	The Effects of Melatonin on Elevated Liver Enzymes During Statins Treatment
NCT03368430	PHASE4	COMPLETED	Melatonin as an Adjunctive Therapy for Chronic Periodontitis.
NCT03419767	PHASE4	UNKNOWN	Insulin Resistance in Patients After Carotid Revascularization
NCT03590197	PHASE4	COMPLETED	Effect of Melatonin on Seizure Outcome, Neuronal Damage and Quality of Life in Patients With Generalized Epilepsy
NCT03631901	PHASE4	COMPLETED	Comparison Between Melatonin and Diazepam for Prevention of Recurrent Simple Febrile Seizures
NCT03689998	PHASE4	COMPLETED	Evaluation of Melatonin Application of Immediate Dental Implant
NCT03831165	PHASE4	COMPLETED	Melatonin Effects on Genital Herpes in Brazilian Women
NCT03945955	PHASE4	COMPLETED	Melatonin and DNA Damage Study
NCT03966235	PHASE4	UNKNOWN	Melatonin on Coronary Artery Calcification
NCT03968939	PHASE4	COMPLETED	Total Joint Arthroplasty and Sleep
NCT04304807	PHASE4	COMPLETED	Effect of Melatonin on Feeding Intolerance and Incidence of Necrotizing Enterocolitis in Preterm Infants
NCT04318067	PHASE4	UNKNOWN	Melatonin in ADHD and Sleep Problems
NCT04864509	PHASE4	UNKNOWN	The Effects of Melatonin Treatment on Bone, Marrow, Sleep and Blood Pressure
NCT04908605	PHASE4	COMPLETED	Emergence Agitation After Nasal Surgery: a Randomized Controlled Comparison Between Melatonin and Mirtazapine

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.

6 molecules share ≥1 primary target. Top 6 by shared-target count:

Molecule	Source	Status	Shared targets
AGOMELATINE	ChEMBL	Phase 4 (approved)	MTNR1A, MTNR1B
CIANIDANOL	ChEMBL	Phase 4 (approved)	MTNR1A, MTNR1B
DOPAMINE	ChEMBL	Phase 4 (approved)	MTNR1A, MTNR1B
RAMELTEON	ChEMBL	Phase 4 (approved)	MTNR1A, MTNR1B
MEBUFOTENIN	ChEMBL	Phase 2	MTNR1A, MTNR1B
TASIMELTEON	ChEMBL + PubChem	Phase 4 (approved)	MTNR1B