HTR2A 5-hydroxytryptamine receptor 2A
ENSG00000102468 · protein coding · Open Targets profile
G protein-coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:1330647, PubMed:18703043, PubMed:19057895, PubMed:21645528, PubMed:22300836, PubMed:35084960, PubMed:38552625). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4- iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD) (PubMed:28129538, PubMed:35084960). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide- binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:28129538, PubMed:35084960). HTR2A 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:28129538, PubMed:35084960). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:28129538, PubMed:35084960). Affects neural activity, perception, cognition and mood (PubMed:18297054). Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction (By similarity). {ECO:0000250|UniProtKB:P35363, ECO:0000269|PubMed:1330647, ECO:0000269|PubMed:18297054, ECO:0000269|PubMed:18703043, ECO:0000269|PubMed:19057895, ECO:0000269|PubMed:21645528, ECO:0000269|PubMed:22300836, ECO:0000269|PubMed:28129538, ECO:0000269|PubMed:35084960, ECO:0000269|PubMed:38552625}.
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 Withdrawn means the drug was pulled from the market or from development.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 0.4517500102519989 (upper bound 0.7062299847602844). 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 120 registry trials, updated in the last three years, of the most advanced drugs against HTR2A (trifluoperazine, haloperidol decanoate, cyclobenzaprine, ziprasidone, chlorpromazine, molindone, chlorprothixene, mesoridazine, loxapine, sarpogrelate, lurasidone, pimavanserin), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- David HuiM.D. Anderson Cancer Center · 4 of 4 trials Phase 2+
- Gregory SullivanTonix Pharmaceuticals, Inc. · 3 of 3 trials Phase 2+
- Denise BedoyaPremier Research · 2 of 2 trials Phase 2+
- Martin BrecherNRx Pharma · 2 of 2 trials Phase 2+
- Alden MilamOrthoCarolina Research Institute, Inc. · 1 of 1 trials Phase 2+
- Andrew A NierenbergHarvard Medical School (HMS and HSDM) · 1 of 1 trials Phase 2+
- Andrew BisharaUCSF Department of Anesthesia · 1 of 1 trials Phase 2+
- Azmi NasserSupernus Pharmaceuticals, Inc. · 1 of 1 trials Phase 2+
- Barbara JachniewiczNurse Practitioner, Department of Surgery · 1 of 1 trials Phase 2+
- Benedicto Crespo FacorroAndalusian Health Service · 1 of 1 trials Phase 2+
- Bjørn H EbdrupUniversity of Copenhagen · 1 of 1 trials Phase 2+
- Christopher JonesCooper University Health Care · 1 of 1 trials Phase 2+
- Ciaran ConsidineVanderbilt University Medical Center · 1 of 1 trials Phase 2+
- Daniel WeintraubCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA · 1 of 1 trials Phase 2+
- David B. YadenJohns Hopkins University · 1 of 1 trials Phase 2+
Registry trials of trifluoperazine, haloperidol decanoate, cyclobenzaprine, ziprasidone, chlorpromazine, molindone, chlorprothixene, mesoridazine, loxapine, sarpogrelate, lurasidone, pimavanserin 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; 98 of 109 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. 11 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
90 trials of drugs against HTR2A were stopped early; 14 give no reason
Terminated, withdrawn and suspended interventional trials of trifluoperazine, haloperidol decanoate, cyclobenzaprine, ziprasidone, chlorpromazine, molindone, chlorprothixene, mesoridazine, loxapine, sarpogrelate, lurasidone, pimavanserin, 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 90.
- terminated · 2026-11-10 · Negovsky Reanimatology Research Institute · matched by the registry's drug synonyms“Financial problems”
- terminated · 2026-09-09 · Apsen Farmaceutica S.A. · Cyclobenzaprine“recruitment difficulty”
- terminated · 2026-05-22 · OrthoCarolina Research Institute, Inc. · matched by the registry's drug synonyms“Low enrollment and subject followup rates”
- terminated · 2026-02-25 · Ohio State University · matched by the registry's drug synonyms“Not able to recruit enough subjects”
- terminated · 2025-12-03 · ACADIA Pharmaceuticals Inc. · Pimavanserin“The study was terminated for business reasons and not due to safety concerns.”
- terminated · 2025-10-02 · Northwestern University · ziprasidone (Geodon)“unable to secure additional funding”
- terminated · 2025-08-24 · ACADIA Pharmaceuticals Inc. · PimavanserinNo reason given
- withdrawn · 2025-07-29 · United States Naval Medical Center, Portsmouth · matched by the registry's drug synonyms“No recruitment occurred and PI retired”
- terminated · 2025-05-21 · Corewell Health South · matched by the registry's drug synonyms“Lost too many patients to follow up, unable to enroll enough patients”
- 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”
- withdrawn · 2024-12-20 · State University of New York - Downstate Medical Center · Pimavanserin“The PI did not have eligible candidates. Therefore, Acadia Pharmaceuticals (the sponsor) closed the study.”
- withdrawn · 2024-12-09 · Bjorn H. Ebdrup · Pimavanserin 34 milligrams (MG) [Nuplazid]“Drug supply withdrawn (dec 2019)”
- terminated · 2024-11-27 · State University of New York - Upstate Medical University · cyclobenzaprine ER (AMRIX)“ran out of funding short of enrollment expected”
- withdrawn · 2024-07-10 · Centre Hospitalier St Anne · CHLORPROMAZINE (CPZ)“No favourable opinion obtained from the Ethics Committee”
- 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.”
- terminated · 2024-05-16 · Supernus Pharmaceuticals, Inc. · matched by the registry's drug synonyms“The program was shut down due to a lack of efficacy.”
- terminated · 2024-04-19 · Marubeni Pharmaceuticals (Suzhou) Co., Ltd. · Lurasidone“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.”
- terminated · 2024-01-31 · Vanderbilt University Medical Center · matched by the registry's drug synonyms“Limitations of the prospective study design revealed that a retrospective study design would be better suited.”
- withdrawn · 2023-12-11 · Tonix Pharmaceuticals, Inc. · matched by the registry's drug synonyms“The study was stopped due to business reasons.”
- terminated · 2023-11-18 · InterveXion Therapeutics, LLC · matched by the registry's drug synonyms“Sponsor decision based on slower than anticipated enrollment leading to fund exhaustion.”
- withdrawn · 2023-03-24 · Baylor College of Medicine · Pimavanserin“Received alternative sources of funding.”
Paediatric incentives and obligations for HTR2A's drugs
For trifluoperazine, haloperidol decanoate, cyclobenzaprine, ziprasidone, chlorpromazine, molindone, chlorprothixene, mesoridazine, loxapine, sarpogrelate, lurasidone, pimavanserin: 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 · HTR2A 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-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-001230-PIP01-11-M05 (Lurasidone hydrochloride, Treatment of schizophrenia): PM: decision on the application for modification of an agreed PIP, 4 Nov 2019; compliance positive 11 Dec 2019; EMEA-001688-PIP03-16 (Pimavanserin, Treatment of schizophrenia and other psychotic disorders): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 2 Dec 2016Rule: 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 trifluoperazine, haloperidol decanoate, cyclobenzaprine, ziprasidone, chlorpromazine, molindone, chlorprothixene, mesoridazine, loxapine, sarpogrelate, lurasidone, pimavanserinRule: 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 · Latuda: authorised since 21 Mar 2014; 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 trifluoperazine, haloperidol decanoate, cyclobenzaprine, ziprasidone, chlorpromazine, molindone, chlorprothixene, mesoridazine, loxapine, sarpogrelate, lurasidone, pimavanserinRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 62 interventional studies of trifluoperazine, haloperidol decanoate, cyclobenzaprine, ziprasidone, chlorpromazine, molindone, chlorprothixene, mesoridazine, loxapine, sarpogrelate, lurasidone, pimavanserin include patients under 18; 3 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, 2026-11-11
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 74 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.