GRIA4 glutamate ionotropic receptor AMPA type subunit 4
ENSG00000152578 · protein coding · Open Targets profile
Ionotropic glutamate receptor that functions as a ligand- gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid (By similarity). L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system and plays an important role in fast excitatory synaptic transmission (By similarity). Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse upon entry of monovalent and divalent cations such as sodium and calcium. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist (By similarity). In the presence of CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of L-glutamate (PubMed:21172611). {ECO:0000250|UniProtKB:P19493, ECO:0000250|UniProtKB:P42262, ECO:0000269|PubMed:21172611}.
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 Withdrawn means the drug was pulled from the market or from development.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, High-Quality Ligand, Druggable Family
- Antibody
- GO CC high conf, UniProt loc med conf, UniProt SigP or TMHMM
- PROTAC
- Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.3269500136375427 (upper bound 0.4352799952030182). 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 92 registry trials, updated in the last three years, of the most advanced drugs against GRIA4 (perampanel, topiramate, osavampator, CX1739, mibampator, tezampanel, zonampanel, farampator, selurampanel, MK-8777, pesampator, becampanel), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Bartolome BurgueraThe Cleveland Clinic · 2 of 2 trials Phase 2+
- mohamed G. Zeinhomneurology department kafr el-sheikh university · 2 of 2 trials Phase 2+
- Aaron KellyUniversity of Minnesota · 1 of 1 trials Phase 2+
- Ali AminaniBariatric Research Medical Director · 1 of 1 trials Phase 2+
- Ali AminianThe Cleveland Clinic · 1 of 1 trials Phase 2+
- BANG-YAN ZHANGNew Taipei Municipal TuCheng Hospital (Built and Operated by Chang Gung Medical Foundation) · 1 of 1 trials Phase 2+
- Bankole A JohnsonUniversity of Virginia · 1 of 1 trials Phase 2+
- Benjamin CanalesUniversity of Florida · 1 of 1 trials Phase 2+
- Carolina S VieiraUniversity of Sao Paulo · 1 of 1 trials Phase 2+
- Casper RokxErasmus Medical Center · 1 of 1 trials Phase 2+
- ChangBeom LeeHanyang Univ. Guri Hospital · 1 of 1 trials Phase 2+
- Charles MarmarNYU Langone Health · 1 of 1 trials Phase 2+
- Christian L RothUniversity of Washington, Dept. of Pediatrics · 1 of 1 trials Phase 2+
- Claudia FoxUniversity of Minnesota · 1 of 1 trials Phase 2+
- Edilberto AmorimUniversity of California, San Francisco · 1 of 1 trials Phase 2+
Registry trials of perampanel, topiramate, osavampator, CX1739, mibampator, tezampanel, zonampanel, farampator, selurampanel, MK-8777, pesampator, becampanel 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; 81 of 86 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.
70 trials of drugs against GRIA4 were stopped early; 8 give no reason
Terminated, withdrawn and suspended interventional trials of perampanel, topiramate, osavampator, CX1739, mibampator, tezampanel, zonampanel, farampator, selurampanel, MK-8777, pesampator, becampanel, 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 70.
- suspended · 2026-10-27 · University of California, Irvine · Topiramate“Enrollment temporarily paused pending IRB continuing review; recruitment expected to resume.”
- terminated · 2026-03-12 · University of Iowa · Topiramate“Lack of funding”
- terminated · 2026-01-22 · Supernus Pharmaceuticals, Inc. · matched by the registry's drug synonyms“Difficulty in recruitment”
- withdrawn · 2025-12-18 · Eurofarma Laboratorios S.A. · ADF1 Group Eurofarma drug association of Sibutramine IR 15mg / Topiramate XR 75mg, ADF2 Group Eurofarma drug association of Sibutramine IR 15mg / Topiramate XR 100mg“Strategic change in development priorities”
- terminated · 2025-10-14 · Wayne State University · Perampanel“Study was not initiated.”
- withdrawn · 2025-05-31 · Janey Pratt · Topiramate“No available funding”
- withdrawn · 2025-04-11 · Stanford University · matched by the registry's drug synonyms“Not funded”
- terminated · 2025-02-28 · VA Office of Research and Development · matched by the registry's drug synonyms“Difficulty recruiting patients”
- withdrawn · 2025-02-14 · University of California, Los Angeles · matched by the registry's drug synonyms“Conducted an interim analysis on similar data”
- suspended · 2025-01-28 · University of Sao Paulo · Topiramate-Implant“We suspended the study for budget issues. It might be resumed in the future.”
- terminated · 2024-09-19 · The Cleveland Clinic · Phentermine / Topiramate Extended Release Oral Capsule“After an unplanned yet IRB approved interim analysis, it was found that there was not a significant difference between the 3 arms of the study. The study was closed due to futility. All Patients are off study and this study will not resume.”
- terminated · 2024-07-31 · University of Florida · matched by the registry's drug synonyms“Poor enrollment”
- terminated · 2024-06-11 · Kristin R Hoffman · Topiramate“The study was stopped early due to changes in the UC Davis guidelines on who qualified for therapeutic hypothermia and significant difficulty in recruitment of patients following the COVID19 pandemic.”
- terminated · 2024-06-06 · Kimford Jay Meador · Perampanel 1 week titration, Perampanel 2 week titration, Perampanel 4mg“Study sponsor no longer provided funding.”
- terminated · 2023-12-14 · Assistance Publique - Hôpitaux de Paris · Perampanel“Lack of inclusion”
- withdrawn · 2023-10-26 · University of Minnesota · matched by the registry's drug synonyms“The project was not funded”
- terminated · 2023-06-22 · Mayo Clinic · Perampanel“The funding sponsor, EISAI, sold the US rights to the medication and can no longer provide it to patients for the study.”
- terminated · 2023-05-06 · Stony Brook University · Perampanel“1) Enrolment below study target and 2) too many subjects had early termination due to disease progression.”
- terminated · 2023-03-23 · VA Office of Research and Development · Topiramate“In ability to recruit”
- terminated · 2023-02-14 · Hartford Hospital · Administration of weight loss drug (Metformin or Topiramate)“Difficulty with enrollment and then Covid pandemic”
- withdrawn · 2022-06-27 · Assistance Publique Hopitaux De Marseille · Perampanel“concomitant decision of the sponsor and the PI, lack of patients”
- terminated · 2022-03-09 · Eisai Inc. · Perampanel“Sponsor's decision”
- terminated · 2022-03-03 · University of Maryland, Baltimore · Topiramate“Principal Investigator was deployed overseas”
- terminated · 2021-09-01 · American University of Beirut Medical Center · matched by the registry's drug synonyms“Study halted due to adverse events”
- terminated · 2021-04-23 · St. Louis University · Topiramate“Lack of enrollment”
Paediatric incentives and obligations for GRIA4's drugs
For perampanel, topiramate, osavampator, CX1739, mibampator, tezampanel, zonampanel, farampator, selurampanel, MK-8777, pesampator, becampanel: 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 · GRIA4 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-000467-PIP01-08-M15 (perampanel, Treatment of treatment-resistant epilepsies): PM: decision on the application for modification of an agreed PIP, 3 Dec 2021; EMEA-000826-PIP01-09 (phentermine;topiramate, Treatment of obesity): W: decision granting a waiver in all age groups for all conditions or indications, 29 Oct 2010Rule: 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/3/24/2932 positive 28 Jun 2024: Treatment of neonatal encephalopathyRule: 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 EU/3/24/2932, 2026-11-11
- Authorised in the EU: yes · Fycompa: authorised since 23 Jul 2012; Qsiva: refusedRule: 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 perampanel, topiramate, osavampator, cx1739, mibampator, tezampanel, zonampanel, farampator, selurampanel, mk-8777, pesampator, becampanelRule: 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 · 98 interventional studies of perampanel, topiramate, osavampator, cx1739, mibampator, tezampanel, zonampanel, farampator, selurampanel, mk-8777, pesampator, becampanel include patients under 18; 5 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 13 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.