Drug Database
ME

melatonin

✓ Approved

Clinigen Group · MTNR1A · Small Molecule

What is melatonin?

melatonin is a small molecule developed by Clinigen Group. It is approved for therapeutic indications via oral (po).

Drug Profile

CompanyClinigen Group
Drug ClassSmall Molecule
Molecular TargetMTNR1A, MTNR1B
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Clinigen Group

Mechanism of Action

Molecular Targets

melatonin acts on 2 molecular targets:

MTNR1Amelatonin receptor 1A (MEL-1A-R, MT1)
MTNR1Bmelatonin receptor 1B (FGQTL2, MT2)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

melatonin is developed for 2 unique indications across 1 therapeutic area.

Therapeutic AreaConditionPhase
Psychiatric disordersInsomnia✓ Approved
Psychiatric disordersSleep disorder✓ Approved

Related Research Articles

PubMedCell communication and signaling : CCS2026-05-24

Melatonin attenuates Mycoplasma pneumoniae-Induced Inflammation and barrier dysfunction by CXCL10/TLR4/STAT1 axis.

Lee Chun-Yi CY, Wu Tsung-Hua TH, Sheu Meei-Ling ML, Chiang Wen-Hsuan WH et al.

Mycoplasma pneumoniae (Mp) is a major pathogen of community-acquired pneumonia increasingly resistant to macrolides. Mp infection provokes oxidative stress, disrupts epithelial integrity, and skews T helper (Th) cell balance through CARDS toxin-mediated immune dysregulation. Here, we investigated the protective effects of melatonin, a pleiotropic hormone with antioxidant and immunomodulatory functions, in patients and a murine model of Mp pneumonia. Mp infection perturbed the local Th1/Th2/Th17 balance, accompanied by ROS accumulation, CXCL10-induced TLR4/STAT1 activation, and loss of ZO1-dependent tight junctions. Melatonin administration suppressed ROS production, restored epithelial barrier integrity, and rebalanced Th responses within the airway microenvironment. Mechanistically, melatonin inhibited CXCL10-TLR4/STAT1 signaling, with TLR4 residue A366 identified as a key regulatory site. These findings reveal that melatonin alleviates Mp-induced airway injury by maintaining immune and epithelial homeostasis, highlighting its potential as an adjunctive therapy for macrolide-resistant Mp pneumonia.

PMID 42177557
Read full article →
PubMedClinica chimica acta; international journal of clinical chemistry2026-05-24

Urinary melatonin: A non-invasive breast cancer biomarker.

Khan Abida A, Alhuthali Hayaa M HM, Alzahrani Shatha S, Alrehaili Amani A AA et al.

Biomarkers of urinary melatonin represent an attractive non-invasive method for enhancing breast cancer diagnosis and follow-up, as they reflect combined circadian physiology in a readily accessible and repeatable urine test. There has been a growing interest in this field, driven by the understanding that melatonin plays a role in regulating the endocrine system, influencing sleep patterns, managing circadian rhythms, affecting exposure to night-time light, and impacting the body's response to cancer and its treatment. The urinary analyte 6-sulfatoxymelatonin has become the most viable surrogate of systemic nocturnal melatonin secretion, due to its increased stability, higher concentration, and suitability for timed, overnight, first-morning, and 24-h urine collection paradigms. Epidemiological, case-control, and longitudinal studies indicate that changes in urinary melatonin levels may be linked to breast cancer risk, disease burden, treatment-associated circadian disruption, and survival-associated sleep impairment. This review aims to present a structured review of the biological foundation, measurement, pre-analytical and analytical determinants, and clinical evidence of urinary melatonin analysis in breast cancer. We compared parent melatonin and 6-sulfatoxymelatonin, assessed immunoassays and chromatographic systems, and discussed significant confounders, such as age, menopausal status, renal function, chronotype, light-at-night exposure, sleep behavior, diet, medications, and sample handling. We further refer to identify the weaknesses that at present clinical translation, such as pre-analytical variability, heterogeneity of assays, absence of reference intervals, and inadequate prospective validation. We believe that the most likely future use of urinary melatonin is as a biomarker component in circadian-informed strategies, where it supplements tumor-specific biomarkers by indicating host physiology, biological time, and treatment-associated circadian disruption.

PMID 42176935
Read full article →
PubMedCancer cell international2026-05-24

Repurposing melatonin for its potential roles in gastrointestinal cancers: highlighting the molecular mechanisms.

Yousefipour Kiana K, Razavi Rohani Seyed Soheil SS, Hosseini Sayed Mohammad Mahdi SMM, Kafilzadeh Kianaz K et al.

Gastrointestinal (GI) cancers are among the most common cancers of the decade, many of which have a poor prognosis. Due to the high prevalence of toxicity and adverse drug reactions (ADRs) of chemotherapeutic agents and low patient compliance, there is always a need for drugs that can be used as adjuvants to existing cancer treatments with low ADRs which can boost the efficacy of chemotherapeutics and reduce the associated toxicities. Repurposing or repositioning a drug with known pharmacological properties is of great value in this context. Drug repurposing has been applied in many illnesses in the recent decade. Melatonin is an endogenous hormone with multiple anticancer properties. It demonstrates antitumor effects by modifying several critical signaling pathways, inhibiting proliferation and metastasis, inducing apoptosis and autophagy, and also reducing oxidative stress. It also reduces toxicity of chemotherapeutics. Due to specific characteristics of melatonin and its limited toxicity, melatonin can be considered as a potential for repositioning in various cancers. Hence, melatonin can be included as an off-label adjuvant chemotherapy to improve the prognosis and overall quality of life of patients suffering from GI cancers. Herein, the action of melatonin on various GI cancers, with the emphasis on its effect on major oncogenic signaling pathways (e.g., Wnt/β-catenin signaling pathway, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), and nuclear factor kappa B (NF-κB)) are discussed. Additionally, mechanisms by which melatonin halts the process of mitosis, induces apoptosis, and makes tumors more vulnerable to chemotherapy are discussed.

PMID 42177485
Read full article →
PubMedCommunications biology2026-05-24

Melatonin attenuates reproductive toxicity of prothioconazole and its metabolite via spermatogenesis and oxidative stress.

Li Jia-Hao JH, Liu Jia-Li JL, Li Ji-Hui JH, Zhou An-Ding AD et al.

Prothioconazole (PTC), a widely used triazole fungicide, and its metabolite, prothioconazole-desthio (dPTC), have been frequently detected in environmental matrices, raising significant concerns regarding their potential adverse effects on mammalian reproductive health. While melatonin has demonstrated protective properties across multiple physiological systems, its efficacy in mitigating PTC- and dPTC-induced reproductive toxicity remains poorly understood. This study investigated the reproductive effects of PTC and dPTC in male mice and evaluated the potential protective effects of melatonin. PTC and dPTC exposure induced reproductive dysfunction, characterized by reduced sperm counts, disrupted spermatogenesis, altered HPG axis hormone secretion, elevated oxidative stress, and compromised BTB integrity. Melatonin co-treatment significantly attenuated these adverse effects, restoring sperm parameters, normalizing HPG axis function, mitigating oxidative stress, and preserving BTB integrity, possibly via the modulation of the MAPK/ERK signaling pathway. These findings underscore the potential reproductive toxicity of PTC/dPTC and propose melatonin as a promising therapeutic approach to alleviate the adverse reproductive impacts induced by triazole fungicides.

PMID 42177336
Read full article →
PubMedEcotoxicology and environmental safety2026-05-24

Melatonin alleviates fluoride-induced developmental neurotoxicity by restoring SIRT3/HIF-1α axis-mediated mitochondrial dysfunction and reversing energy metabolism reprogramming.

Ma Runjiang R, Wang Chun C, Qin Wenqi W, Yan Chulin C et al.

Excessive fluoride exposure causes developmental neurotoxicity, but the mechanism linking fluoride to neuronal energy metabolism disorders-especially via mitochondrial function-remains elusive. Here, we investigated whether the SIRT3/HIF-1α axis mediates fluoride-induced developmental neurotoxicity and if melatonin (Mel) mitigates this by targeting energy metabolism. In vivo, Sprague-Dawley rats were perinatally exposed to sodium fluoride (NaF: 10, 20, 40 mg/kg/day) with/without Mel (10 mg/kg/day); in vitro, HT22 cells were treated with NaF (0, 20, 40, 60 mg/L) and/or Mel (20 μmol/L), or transfected with HIF-1α siRNA. Results demonstrated that NaF suppressed SIRT3 expression, resulting in mitochondrial dysfunction and reactive oxygen species (ROS) accumulation. Elevated ROS upregulated HIF-1α, shifting cellular energy metabolism from oxidative phosphorylation (OXPHOS) toward glycolysis. This metabolic reprogramming was evidenced by decreased oxygen consumption rate (OCR) and NDUFS1 expression, alongside increased extracellular acidification rate (ECAR), upregulation of PFKFB3, PKM2, and LDHA, and elevated pyruvate and lactate levels. These changes ultimately led to reduced ATP production and cognitive impairment in offspring rats. Notably, Mel attenuated NaF-induced mitochondrial dysfunction by upregulating SIRT3 and inhibiting HIF-1α, thereby restoring OXPHOS and increasing ATP levels. Furthermore, HIF-1α silencing similarly reversed NaF-induced disruptions in energy metabolism. Our findings reveal a novel mechanism for NaF-induced developmental neurotoxicity and highlight the potential of Mel as a protective agent against environmental fluoride exposure.

PMID 42176635
Read full article →
PubMedBMC plant biology2026-05-24

Integrated transcriptomic and metabolomic analyses reveal melatonin-mediated drought response in red raspberry at the squaring stage.

Guo Juanjuan J, Cheng Siqi S, Fu Ziqian Z, Dong Qinglong Q et al.

Red raspberry (Rubus idaeus L.) cultivation is often constrained by drought stress, which reduces fruit yield and quality. Melatonin (MT) plays an important role in plant stress tolerance. This study examined how exogenous MT improves drought tolerance in red raspberry at the squaring stage. It focused on changes in photosynthetic performance, antioxidant capacity, leaves anatomical structure, gene expression, and hormone homeostasis. Drought stress significantly reduced photosynthetic performance, antioxidant enzyme activities, and hormone homeostasis in red raspberry, and altered leaves anatomical structure. Exogenous MT treatment, particularly at 150 μmol L⁻1, effectively alleviated these drought-induced effects. MT increased net photosynthetic rate and stomatal conductance, reduced oxidative damage, and promoted osmotic accumulation. At the anatomical level, MT-treated leaves showed more compact spongy tissue, increased palisade tissue and leaves thickness under drought stress. Transcriptomic and metabolomic analyses further revealed coordinated molecular changes under MT treatment. These changes mainly involved photosynthesis, carbohydrate and starch metabolism, plant hormone signaling, and amino acid metabolism. Genes related to photosynthetic function (PNSL3 and PNSB4), carbohydrate metabolism (glgc and PYG), antioxidant defense (SOD1 and sodC), and auxin signaling (AUX1 and SAUR) showed marked expression changes under MT treatment. Metabolite profiling also revealed changes in sugars, amino acids, phenolic compounds, and hormone-related compounds. Several transcription factor families, including bHLH, MYB-related, NAC, WRKY, and ERF, showed strong responses to MT. These changes were associated with transcriptional regulation and metabolic adjustment under drought stress. Exogenous MT significantly improved drought tolerance in red raspberry at the squaring stage, with 150 μmol L⁻1 showing the best overall performance. This protective effect was associated with improved photosynthetic performance, enhanced antioxidant capacity, and better maintenance of leaves structure. Integrated transcriptomic and metabolomic analyses further revealed changes in hormone-related and metabolic pathways. These findings indicate that MT enhanced drought tolerance in red raspberry through coordinated physiological, anatomical, and molecular responses.

PMID 42177410
Read full article →

+9996 more articles available with a free account

Sign up free to view all articles →

Ask about melatonin