HCRTR1 hypocretin receptor 1
ENSG00000121764 · protein coding · Open Targets profile
G protein-coupled receptor that binds the neuropeptide orexin-A with high affinity, and orexin-B with lower affinity, two peptides derived from a common precursor, prepro-orexin (PubMed:32669442, PubMed:9491897). Its activity is mediated via a G(q)- protein-coupled pathway, which activates the phosphatidylinositol- calcium second messenger system in response to orexin-A binding (PubMed:32669442). In addition to G(q)-mediated signaling, orexin-A stimulation also promotes beta-arrestin recruitment, leading to receptor internalization (PubMed:15683363, PubMed:32669442). Plays a significant role in the regulation of food intake (By similarity). {ECO:0000250|UniProtKB:P56718, ECO:0000269|PubMed:15683363, ECO:0000269|PubMed:32669442, ECO:0000269|PubMed:9491897}.
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 Withdrawn means the drug was pulled from the market or from development.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
- UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM
- PROTAC
- Small Molecule Binder
- Other modalities
- Advanced Clinical
gnomAD loss of function constraint: o/e 0.689490020275116 (upper bound 0.9453099966049194). 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 90 registry trials, updated in the last three years, of the most advanced drugs against HCRTR1 (daridorexant, lemborexant, suvorexant, almorexant, ORN-0829 HYDRATE, SB-649868, filorexant), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Andrew S HuhnJohns Hopkins University · 2 of 2 trials Phase 2+
- Brendan LuceyWashington Univeristy School of Medicine · 2 of 2 trials Phase 2+
- Jennifer EllisJohns Hopkins University · 2 of 2 trials Phase 2+
- John W WinkelmanMassachusetts General Hospital · 2 of 2 trials Phase 2+
- Sabra S InslichtSan Francisco VA Medical Center, San Francisco, CA · 2 of 2 trials Phase 2+
- Sarocha VivatvakinDepartment of Medicine, Faculty of Medicine · 2 of 2 trials Phase 2+
- Abisith DechachongjumroenPhramongkutklao hospital and College of Medicine · 1 of 1 trials Phase 2+
- Andrew D KrystalUniversity of California, San Francisco · 1 of 1 trials Phase 2+
- Angelo SambunarisInstitute for Advanced Medical Research · 1 of 1 trials Phase 2+
- Antonio Y. HardanStanford University · 1 of 1 trials Phase 2+
- Aric PratherUniversity of California, San Francisco · 1 of 1 trials Phase 2+
- Balachundhar SubramaniamBeths Israel Deaconess Medical Center · 1 of 1 trials Phase 2+
- Brendon YeeWoolcock Institute of Medical Research · 1 of 1 trials Phase 2+
- Caitlin E MartinVirginia Commonwealth University Institute for Drug and Alcohol Studies · 1 of 1 trials Phase 2+
- Camilla HoyosWoolcock Institute of Medical Research · 1 of 1 trials Phase 2+
Registry trials of daridorexant, lemborexant, suvorexant, almorexant, ORN-0829 HYDRATE, SB-649868, filorexant 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; 79 of 84 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. 6 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
15 trials of drugs against HCRTR1 were stopped early
Terminated, withdrawn and suspended interventional trials of daridorexant, lemborexant, suvorexant, almorexant, ORN-0829 HYDRATE, SB-649868, filorexant, 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 15 most recent of 15.
- terminated · 2026-11-04 · Institute for Advanced Medical Research, Alpharetta, GA · suvorexant“inability to recruit volunteers”
- terminated · 2026-08-12 · Medical University of South Carolina · Suvorexant Tablets“Terminated early due to insufficient accrual to meet prespecified statistical analysis requirements.”
- terminated · 2026-07-30 · Unity Health Toronto · Lemborexant“Funding withdrawn by sponsor.”
- suspended · 2026-06-30 · Global Coalition for Adaptive Research · Intervention C Daridorexant“The trial has been temporarily suspended due to administrative issues”
- suspended · 2026-06-30 · Global Coalition for Adaptive Research · Intervention C Daridorexant“The trial has been temporarily suspended due to administrative issues”
- terminated · 2026-05-28 · Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal · Lemborexant 5 MG [Dayvigo]“In agreement with all parties, the project was closed on March 31 due to recruitment challenges.”
- withdrawn · 2025-05-01 · Mayo Clinic · Suvorexant“low/slow accrual”
- terminated · 2025-04-29 · The University of Texas Health Science Center, Houston · suvorexant (SUVO)“Lack of enrollment”
- terminated · 2024-09-25 · Wayne State University · Suvorexant, Suvorexant Placebo“Did not meet enrollment goals.”
- withdrawn · 2023-11-08 · Brendan Lucey · Lemborexant 25 mg“Study was terminated due to enrollment difficulties and the inability to obtain necessary study supplies. Five participants signed consent; however, no one was randomized. The study was officially terminated with the funding source on 10/04/2023.”
- terminated · 2023-02-15 · The Florey Institute of Neuroscience and Mental Health · Suvorexant 20 mg“Recruitment problems during covid lockdowns resulted in Merck ceasing supply of suvorexant/placebo”
- terminated · 2021-06-16 · Henry Ford Health System · suvorexant“reduced ability to recruit sufficient number of patients”
- withdrawn · 2021-02-21 · Massachusetts General Hospital · Suvorexant (Belsomra)“Study was terminated due to COVID-19.”
- terminated · 2018-11-07 · Merck Sharp & Dohme LLC · Filorexant“Low Enrollment”
- withdrawn · 2015-04-17 · GlaxoSmithKline · SB-649868“The study was stoppend before recruitment start for preclinical safety finding in rats.”
Paediatric incentives and obligations for HCRTR1's drugs
For daridorexant, lemborexant, suvorexant, almorexant, ORN-0829 HYDRATE, SB-649868, filorexant: 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 · HCRTR1 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 · EMA/PE/0000233864 (Daridorexant, Treatment of insomnia): PM: decision on the application for modification of an agreed PIP, 16 Apr 2025Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA EMA/PE/0000233864, 2026-11-11
- EU orphan designation: no · No EU orphan designation names daridorexant, lemborexant, suvorexant, almorexant, orn-0829 hydrate, sb-649868, filorexantRule: 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 · Quviviq: authorised since 29 Apr 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 EPAR Quviviq, 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 daridorexant, lemborexant, suvorexant, almorexant, orn-0829 hydrate, sb-649868, filorexantRule: 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 · 3 interventional studies of daridorexant, lemborexant, suvorexant, almorexant, orn-0829 hydrate, sb-649868, filorexant include patients under 18; 2 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 8 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.