MTNR1A melatonin receptor 1A
ENSG00000168412 · protein coding · Open Targets profile
High affinity receptor for melatonin. Likely to mediate the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity. Possibly involved in sleep induction, by melatonin activation of the potassium channel KCNMA1/BK and the dissociation of G-beta and G-gamma subunits, thereby decreasing synaptic transmission (By similarity). .
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, Druggable Family
- Antibody
- GO CC high conf, UniProt loc med conf, UniProt SigP or TMHMM
- PROTAC
- Small Molecule Binder
gnomAD loss of function constraint: o/e 1.2755999565124512 (upper bound 2.3959999084472656). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 289 registry trials, updated in the last three years, of the most advanced drugs against MTNR1A (tasimelteon, melatonin, ramelteon, piromelatine), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Christina BarkauskasDuke Clinical Research Institute · 2 of 2 trials Phase 2+
- Lon SchneiderKeck School of Medicine of USC, Los Angeles, CA · 2 of 2 trials Phase 2+
- Sriram YennuMD Anderson · 2 of 2 trials Phase 2+
- Susan RedlineBrigham and Women's Hospital · 2 of 2 trials Phase 2+
- Patricia FRANCOService Épilepsie-Sommeil-Explorations Fonctionnelles Neurologiques Pédiatriques, Hôpital Femme-Mère-Enfant, Hospices Civils de Lyon · 1 of 2 trials Phase 2+
- Alexa HollingerUniversity Hospital, Basel, Switzerland · 1 of 1 trials Phase 2+
- Antonio Carrillo VicoInstitute of Biomedicine of Seville (IBiS) · 1 of 1 trials Phase 2+
- Arash L AfshariCopenhagen University Hospital, Rigshospitalet · 1 of 1 trials Phase 2+
- Assoc. Prof. Premjit JuntongjinChulabhorn International College of Medicine, Thammasat University · 1 of 1 trials Phase 2+
- Aya GAE IsmaeilFaculty of Medicine, Tanta University, Egypt · 1 of 1 trials Phase 2+
- Carol TammingaUniversity of Texas Southwestern Medical Center · 1 of 1 trials Phase 2+
- Chin-Bin YehTri-Service General Hospital (TSGH) · 1 of 1 trials Phase 2+
- Clara M Rosso FernándezClinical Research and Clinical Trials Unit (Virgen del Rocío University Hospital, Seville) · 1 of 1 trials Phase 2+
- Cydni WilliamsOregon Health and Science University · 1 of 1 trials Phase 2+
- Daisy Evangeline C GarciaIlocos Training and Regional Medical Center · 1 of 1 trials Phase 2+
Registry trials of tasimelteon, melatonin, ramelteon, piromelatine updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 258 of 267 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 22 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
84 trials of drugs against MTNR1A were stopped early; 9 give no reason
Terminated, withdrawn and suspended interventional trials of tasimelteon, melatonin, ramelteon, piromelatine, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 84.
- terminated · 2026-09-09 · Neurim Pharmaceuticals Ltd. · Piromelatine 20 mg“Treatment with 20 mg piromelatine did not demonstrate efficacy over treatment with placebo based on analysis with the ADAS-Cog 14 subscale and with other cognitive and neuropsychiatric parameters.”
- terminated · 2026-02-20 · Fundación Pública Andaluza para la gestión de la Investigación en Sevilla · Melatonin“Early termination due to operational feasibility reasons, resulting from a slow recruitment rate and logistical and financial difficulties that prevent reaching the planned sample size within the study schedule.”
- withdrawn · 2025-12-24 · University of Colorado, Denver · matched by the registry's drug synonyms“Study PI Moved Institutions”
- terminated · 2025-10-09 · Brigham and Women's Hospital · Tasimelteon“Study will not longer be done. Terminated due to sponsor noncompliance.”
- withdrawn · 2025-04-11 · Stanford University · Melatonin 5 mg“Investigator elected not to proceed with project”
- terminated · 2025-02-05 · Douglas Mental Health University Institute · Melatonin“Lack of funding”
- withdrawn · 2024-09-03 · University of Nebraska · Melatonin“Study never started”
- terminated · 2024-06-06 · Stony Brook University · Melatonin and Donepezil“too few subjects enrolled”
- terminated · 2024-05-29 · Mayo Clinic · matched by the registry's drug synonyms“Slow enrollment”
- terminated · 2024-02-07 · State University of New York at Buffalo · Melatonin“difficult recruitment and complete first visit in person during thne hight of tne pandemic and later not enough subjects”
- withdrawn · 2024-01-26 · University of Florida · matched by the registry's drug synonyms“study never started”
- terminated · 2024-01-09 · Northwestern University · matched by the registry's drug synonyms“Low subject recruitment and enrollment.”
- terminated · 2023-10-13 · Amy Gelfand · Melatonin“Insufficient Fund”
- terminated · 2023-09-08 · University of Nebraska · matched by the registry's drug synonyms“Unsuccessful in recruiting appropriate subjects.”
- withdrawn · 2023-07-20 · AGUNCO Obstetrics and Gynecology Centre · matched by the registry's drug synonymsNo reason given
- terminated · 2023-05-30 · Rockefeller University · matched by the registry's drug synonyms“Interrupted by Covid-19”
- terminated · 2023-03-30 · Virginia Commonwealth University · Melatonin“Lack of efficacy”
- terminated · 2022-12-29 · University of Sao Paulo · Ramelteon (RozeremR)“Takeda suspended financial support. The first phase (observational study) is ongoing.”
- terminated · 2022-12-22 · University of Michigan · matched by the registry's drug synonyms“Funding no longer available”
- withdrawn · 2022-07-22 · State University of New York at Buffalo · Melatonin“lack of subject enrollment”
- withdrawn · 2022-07-14 · Institution de Lavigny · melatonin“The study did not received the approbation from Swissmedic. Therefore, the recruitment of participants never started.”
- terminated · 2022-06-13 · Centre Jean Perrin · melatonin“The study stopped for futility after the DSMB.”
- suspended · 2022-06-03 · The University of Hong Kong · Melatonin“Unable to secure study medication supply”
- terminated · 2022-03-21 · Yale University · Melatonin“Lack of resources to complete the study. Descriptive statistics for the outcome measures collected are provided.”
- withdrawn · 2021-11-15 · University of Alberta · matched by the registry's drug synonyms“Issues surrounding the current COVID-19 pandemic.”
Paediatric incentives and obligations for MTNR1A's drugs
For tasimelteon, melatonin, ramelteon, piromelatine: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · MTNR1A is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-001531-PIP01-13-M06 (tasimelteon, Treatment of disorders of the sleep-wake schedule): PM: decision on the application for modification of an agreed PIP, 13 Sept 2024; EMEA-000440-PIP02-11-M05 (melatonin, Treatment of insomnia): PM: decision on the application for modification of an agreed PIP, 6 Apr 2017; compliance positive 21 Apr 2017; EMEA-000440-PIP01-08 (melatonin, Primary insomnia): RW: decision refers to a refusal on a request for waiver in all age groups for the listed condition(s), 24 Mar 2009Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/10/841 expired 23 Feb 2011: Treatment of non-24-hour sleep-wake disorders in blind people with no light perception; EU/3/12/978 positive 2 Apr 2012: Treatment of perinatal asphyxia; EU/3/23/2832 positive 13 Oct 2023: Treatment of Smith-Magenis syndrome; EU/3/23/2757 positive 15 Feb 2023: Treatment of perinatal asphyxia; +17 moreRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Slenyto: authorised since 20 Sept 2018; Hetlioz: authorised since 3 Jul 2015; Circadin: authorised since 29 Jun 2007; Melatonin Neurim: authorised since 7 Nov 2022Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of tasimelteon, melatonin, ramelteon, piromelatineRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 145 interventional studies of tasimelteon, melatonin, ramelteon, piromelatine include patients under 18; 35 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-12
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 5 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.