HTR2C 5-hydroxytryptamine receptor 2C
ENSG00000147246 · protein coding · Open Targets profile
G protein-coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:12970106, PubMed:18703043, PubMed:19057895, PubMed:29398112, PubMed:7895773). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD) (PubMed:19057895, PubMed:29398112). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:18703043, PubMed:29398112). HTR2C is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers that modulate the activity of phosphatidylinositol 3-kinase and promote the release of Ca(2+) ions from intracellular stores, respectively (PubMed:18703043, PubMed:29398112). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:29398112). Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelanocortin neurons and the release of CRH that then regulates the release of corticosterone (By similarity). Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress (By similarity). Plays a role in insulin sensitivity and glucose homeostasis (By similarity). {ECO:0000250|UniProtKB:P34968, ECO:0000269|PubMed:12970106, ECO:0000269|PubMed:18703043, ECO:0000269|PubMed:19057895, ECO:0000269|PubMed:29398112, ECO:0000269|PubMed:7895773}.
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 Withdrawn means the drug was pulled from the market or from development.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
gnomAD loss of function constraint: o/e 0.23754000663757324 (upper bound 0.49946001172065735). 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 229 registry trials, updated in the last three years, of the most advanced drugs against HTR2C (chlorprothixene, trimipramine, clothiapine, trifluoperazine, trazodone, ziprasidone, loxapine, olanzapine pamoate, cyclobenzaprine, methysergide, methixene, quetiapine), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Gregory SullivanTonix Pharmaceuticals, Inc. · 3 of 3 trials Phase 2+
- David McDonnellAlkermes, Inc. · 2 of 3 trials Phase 2+
- Denise BedoyaPremier Research · 2 of 2 trials Phase 2+
- F. Markus LewekeCentral Institute of Mental Health · 2 of 2 trials Phase 2+
- Juan WangSecond Affiliated Hospital, Zhejiang University, School of Medicine · 2 of 2 trials Phase 2+
- Kavita JunejaCorcept Therapeutics · 2 of 2 trials Phase 2+
- M Safwan BadrJohn D. Dingell VA Medical Center, Detroit, MI · 2 of 2 trials Phase 2+
- Aimee RolstonUniversity of Michigan Rogel Cancer Center · 1 of 1 trials Phase 2+
- Alden MilamOrthoCarolina Research Institute, Inc. · 1 of 1 trials Phase 2+
- Aminah JatoiMayo Clinic · 1 of 1 trials Phase 2+
- Anders Fink-JensenPsychiatric Centre Copenhagen. University of Copenhagen. · 1 of 1 trials Phase 2+
- Andre TappVA Puget Sound Health Care System, Tacoma and Seattle, WA and University of Washington, Department of Psychiatry and Behavioral Sciences, Seattle, WA · 1 of 1 trials Phase 2+
- Andrew BisharaUCSF Department of Anesthesia · 1 of 1 trials Phase 2+
- Anurag K SinghRoswell Park Cancer Institute · 1 of 1 trials Phase 2+
- Aslam EjazUniversity of Illinois at Chicago (UIC) · 1 of 1 trials Phase 2+
Registry trials of chlorprothixene, trimipramine, clothiapine, trifluoperazine, trazodone, ziprasidone, loxapine, olanzapine pamoate, cyclobenzaprine, methysergide, methixene, quetiapine 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; 190 of 209 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. 20 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
149 trials of drugs against HTR2C were stopped early; 14 give no reason
Terminated, withdrawn and suspended interventional trials of chlorprothixene, trimipramine, clothiapine, trifluoperazine, trazodone, ziprasidone, loxapine, olanzapine pamoate, cyclobenzaprine, methysergide, methixene, quetiapine, 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 149.
- terminated · 2026-11-05 · Dr. Inge Winter · Quetiapine“The site in Israel stopped recruitment due to logistic reasons. Other sites are recruiting for 2023-506602-39-00, 2023-506605-19-00, 2023-506617-21-00.”
- terminated · 2026-09-14 · Denovo Biopharma LLC · Quetiapine“The decision to stop the trial was based on efficacy results in the overall schizophrenia participant population.”
- terminated · 2026-09-09 · Apsen Farmaceutica S.A. · Cyclobenzaprine“recruitment difficulty”
- terminated · 2026-09-02 · The Guthrie Clinic · matched by the registry's drug synonyms“Study stopped due to lower than expected accrual.”
- withdrawn · 2026-07-28 · Icahn School of Medicine at Mount Sinai · matched by the registry's drug synonyms“Enrollment was discontinued after limited accrual prevented feasible completion of the trial.”
- terminated · 2026-05-22 · OrthoCarolina Research Institute, Inc. · matched by the registry's drug synonyms“Low enrollment and subject followup rates”
- withdrawn · 2026-05-04 · University of Southern California · Trazodone, Quetiapine“PI left institution. Study never started.”
- terminated · 2026-02-25 · Ohio State University · matched by the registry's drug synonyms“Not able to recruit enough subjects”
- terminated · 2025-10-02 · Northwestern University · ziprasidone (Geodon)“unable to secure additional funding”
- terminated · 2025-06-24 · Third People's Hospital, Huzhou City, Zhejiang Province, China · matched by the registry's drug synonyms“the sponsor has determined that access to the full dataset is no longer available”
- terminated · 2025-06-18 · University of Michigan Rogel Cancer Center · matched by the registry's drug synonyms“Lack of Patient Population”
- terminated · 2025-05-22 · Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León · Quetiapine 25 milligrams capsule“Due to the crisis SARS-COV-2 pandemic: recruitment of patients for the trial is stopped, healthcare pressure generated, suspend the non-essential scheduled surgical activity and on June 30, 2020 medication expired, funding has been exhausted.”
- withdrawn · 2025-04-27 · Janssen-Cilag International NV · Trazodone Prolonged Release“New design was developed to better fit company strategy, a new study has replaced 5413541TRD3011 study”
- withdrawn · 2025-04-04 · Verinder Sharma · Trazodone“This study was pivoted to be a randomized control trial of trazodone versus quetiapine, under a new NTC identification number (study protocol number 125638).”
- terminated · 2025-02-25 · Tonix Pharmaceuticals, Inc. · matched by the registry's drug synonyms“For business reason unrelated to safety or tolerability,Tonix discontinued this study.”
- terminated · 2025-02-06 · Tonix Pharmaceuticals, Inc. · matched by the registry's drug synonyms“Stopped early due to inadequate separation on primary efficacy endpoint in the lead-in HONOR study, TNX-CY-P301”
- terminated · 2025-02-06 · Tonix Pharmaceuticals, Inc. · matched by the registry's drug synonyms“Interim Analysis results”
- terminated · 2024-12-27 · Central Institute of Mental Health, Mannheim · matched by the registry's drug synonyms“Following the expiry of the original research grant, no follow-up financing could be provided to complete the study.”
- terminated · 2024-11-27 · State University of New York - Upstate Medical University · cyclobenzaprine ER (AMRIX)“ran out of funding short of enrollment expected”
- terminated · 2024-05-28 · Assistance Publique - Hôpitaux de Paris · Intramuscular loxapine“Sponsor decision:”
- terminated · 2024-05-22 · Tonix Pharmaceuticals, Inc. · matched by the registry's drug synonyms“Stopped early due to inadequate separation on primary efficacy endpoint at Week 12 according to Interim Analysis conducted on the first 274 (50%) patients.”
- withdrawn · 2024-05-06 · Mayo Clinic · matched by the registry's drug synonyms“Closed due to slow accrual”
- terminated · 2024-04-23 · Mylan Pharmaceuticals Inc · matched by the registry's drug synonyms“during Period 1 due to numerous orthostatic AEs that occurred. Subsequently, RLD was reduced to 5 mg due to safety concerns.”
- terminated · 2024-04-19 · Marubeni Pharmaceuticals (Suzhou) Co., Ltd. · matched by the registry's drug synonyms“Company's business decision”
- withdrawn · 2024-02-28 · Eurofarma Laboratorios S.A. · FDC of etoricoxib + cyclobenzaprine + etoricoxib placebo, cyclobenzaprine hydrochloride + etoricoxib placebo“Change in study strategy.”
Paediatric incentives and obligations for HTR2C's drugs
For chlorprothixene, trimipramine, clothiapine, trifluoperazine, trazodone, ziprasidone, loxapine, olanzapine pamoate, cyclobenzaprine, methysergide, methixene, quetiapine: 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 · HTR2C 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-002142-PIP01-17 (trazodone (hydrochloride), Treatment of insomnia): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 19 Dec 2017; EMEA-001115-PIP01-10-M08 (loxapine, Treatment of bipolar disorder;Treatment of schizophrenia): PM: decision on the application for modification of an agreed PIP, 10 Jun 2023; EMEA-002263-PIP01-17 (trazodone (hydrochloride);gabapentin, Treatment of painful diabetic neuropathy): W: decision granting a waiver in all age groups for all conditions or indications, 16 Mar 2018Rule: 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: no · No EU orphan designation names chlorprothixene, trimipramine, clothiapine, trifluoperazine, trazodone, ziprasidone, loxapine, olanzapine pamoate, cyclobenzaprine, methysergide, methixene, quetiapineRule: 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 · Zypadhera: authorised since 19 Nov 2008; Adasuve: authorised since 20 Feb 2013Rule: 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 chlorprothixene, trimipramine, clothiapine, trifluoperazine, trazodone, ziprasidone, loxapine, olanzapine pamoate, cyclobenzaprine, methysergide, methixene, quetiapineRule: 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 · 118 interventional studies of chlorprothixene, trimipramine, clothiapine, trifluoperazine, trazodone, ziprasidone, loxapine, olanzapine pamoate, cyclobenzaprine, methysergide, methixene, quetiapine include patients under 18; 9 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 44 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.