GABBR1 gamma-aminobutyric acid type B receptor subunit 1
ENSG00000204681 · protein coding · Open Targets profile
Component of a heterodimeric G protein-coupled receptor for GABA, formed by GABBR1 and GABBR2 (PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054, PubMed:36103875, PubMed:9872316, PubMed:9872744). Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins (PubMed:18165688). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase (PubMed:10075644, PubMed:10773016, PubMed:10906333, PubMed:24305054, PubMed:9872744). Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis (PubMed:10075644). Calcium is required for high affinity binding to GABA (By similarity). Plays a critical role in the fine- tuning of inhibitory synaptic transmission (PubMed:9844003). Pre- synaptic GABA receptor inhibits neurotransmitter release by down- regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials (PubMed:10075644, PubMed:22660477, PubMed:9844003, PubMed:9872316, PubMed:9872744). Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception (Probable). Activated by (-)-baclofen, cgp27492 and blocked by phaclofen (PubMed:24305054, PubMed:9844003, PubMed:9872316). {ECO:0000250|UniProtKB:Q9Z0U4, ECO:0000269|PubMed:10075644, ECO:0000269|PubMed:10773016, ECO:0000269|PubMed:10906333, ECO:0000269|PubMed:15617512, ECO:0000269|PubMed:18165688, ECO:0000269|PubMed:22660477, ECO:0000269|PubMed:24305054, ECO:0000269|PubMed:36103875, ECO:0000269|PubMed:9844003, ECO:0000269|PubMed:9872316, ECO:0000269|PubMed:9872744, ECO:0000305}.
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 Withdrawn means the drug was pulled from the market or from development.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 loc med conf, UniProt SigP or TMHMM
- PROTAC
- Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.29750001430511475 (upper bound 0.394430011510849). 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 55 registry trials, updated in the last three years, of the most advanced drugs against GABBR1 (sodium oxybate, baclofen, oxybate, arbaclofen, arbaclofen placarbil, lesogaberan, SGS-742), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Andréane Richard-DenisCIUSSS du Nord-de-l'île-de-Montréal-Hôpital du Sacré-Cœur de Montréal · 1 of 1 trials Phase 2+
- Andrew BisharaUCSF Department of Anesthesia · 1 of 1 trials Phase 2+
- Aya MoussaTanta University · 1 of 1 trials Phase 2+
- Carolyn LevisMcMaster University · 1 of 1 trials Phase 2+
- Chad RuoffMayo Clinic · 1 of 1 trials Phase 2+
- Craig A. EricksonChildren's Hospital Medical Center, Cincinnati · 1 of 1 trials Phase 2+
- Evdokia AnagnostouHolland Bloorview Kids Rehabilitation Hospital · 1 of 1 trials Phase 2+
- Florian ThomasSeton Hall-Hackensack-Meridian School of Medicine, Hackensack, USA · 1 of 1 trials Phase 2+
- Giuseppe ValenteMcMaster University · 1 of 1 trials Phase 2+
- Jean-François CIAISCentre Hospitalier Princesse Grace - Monaco · 1 of 1 trials Phase 2+
- Julia FreiMcMaster University, Offord Centre for Child Studies · 1 of 1 trials Phase 2+
- Karen L CropseyUniversity of Alabama at Birmingham · 1 of 1 trials Phase 2+
- Marianne de VisserAcademic Medical Center, Amsterdam, Netherlands · 1 of 1 trials Phase 2+
- Mario SaportaUniversity of Miami Miller School of Medicine, USA · 1 of 1 trials Phase 2+
- Mark MandabachUniversity of Alabama at Birmingham · 1 of 1 trials Phase 2+
Registry trials of sodium oxybate, baclofen, oxybate, arbaclofen, arbaclofen placarbil, lesogaberan, SGS-742 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; 45 of 51 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. 4 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
33 trials of drugs against GABBR1 were stopped early; 3 give no reason
Terminated, withdrawn and suspended interventional trials of sodium oxybate, baclofen, oxybate, arbaclofen, arbaclofen placarbil, lesogaberan, SGS-742, 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 33.
- terminated · 2026-01-07 · University of Alabama at Birmingham · Baclofen 5 mg, Baclofen 10mg“No funding for this project”
- terminated · 2025-12-16 · University Hospital, Lille · Baclofen“DEFAULT OF INCLUSION”
- withdrawn · 2024-09-19 · University of Alberta · Baclofen“Study recruitment was halted due to restrictions and we have decided to not pursue it further.”
- terminated · 2024-09-05 · University of Alabama at Birmingham · Baclofen 10mg“Futility analysis at midpoint analysis”
- withdrawn · 2022-12-15 · University Hospital, Ghent · Sodium oxybate“incompatibilities over intellectual property”
- terminated · 2022-04-29 · Mansoura University · Baclofen“COVID 19 Pandemic”
- withdrawn · 2022-04-27 · RVL Pharmaceuticals, Inc. · arbaclofen ER Tablets, Placebo for arbaclofen ER tablets“suspended due to inability to enroll subjects”
- withdrawn · 2021-03-04 · Brigham and Women's Hospital · Sodium Oxybate Oral Solution [Xyrem]“Target study population was extremely difficult to recruit and planned study budget was exceeded”
- terminated · 2019-03-20 · University of Michigan · matched by the registry's drug synonyms“Terminated prematurely due to feasibility issues with rate of recruitment”
- terminated · 2018-12-31 · Shaare Zedek Medical Center · oral baclofen + placebo, placebo + oral baclofen“Lack of funding”
- terminated · 2018-08-14 · Wake Forest University Health Sciences · Baclofen“recruitment was going too slowly”
- terminated · 2018-05-23 · Denver Health and Hospital Authority · Baclofen“Insufficient funding to complete with low enrollment rate”
- withdrawn · 2018-02-23 · Tufts Medical Center · sodium oxybate“Sponsor pulled funding secondary to economy issues”
- withdrawn · 2017-08-29 · Boston Children's Hospital · Baclofen“No participants were enrolled”
- terminated · 2017-05-05 · Essentia Health · Baclofen“The enrollment in the study was too limited for meaningful data analysis.”
- withdrawn · 2016-10-06 · University of Missouri-Columbia · baclofen, intrathecal“No subjects enrolled.”
- withdrawn · 2016-09-08 · University of Pennsylvania · Baclofen ER“This study never started due to delays in medication development”
- terminated · 2016-05-19 · University of Medicine and Dentistry of New Jersey · Sodium Oxybate“Withdrawal of support.”
- suspended · 2016-05-13 · University of Liege · BaclofenNo reason given
- terminated · 2015-11-04 · VA Office of Research and Development · Baclofen“Enrollment was completed with insufficient sample size for publishable results”
- terminated · 2015-08-21 · Gonzalez-Heydrich, Joseph, M.D. · R-baclofen“too much variability in the TMS measures”
- withdrawn · 2015-03-06 · Flowonix Medical · matched by the registry's drug synonyms“Study was never started. Full IDE-approval not obtained. new IDE will be submitted”
- withdrawn · 2014-05-16 · University of Manitoba · Baclofen“The study have been stoped because the protocol is going to be modify.”
- terminated · 2013-09-12 · Centre for Addiction and Mental Health · Baclofen 30 mg/day, Baclofen 60 mg/day“The study was terminated because of difficulties recruiting subjects.”
- terminated · 2013-07-31 · Seaside Therapeutics, Inc. · STX209 (arbaclofen)No reason given
Paediatric incentives and obligations for GABBR1's drugs
For sodium oxybate, baclofen, oxybate, arbaclofen, arbaclofen placarbil, lesogaberan, SGS-742: 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 · GABBR1 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-001549-PIP02-14 (baclofen, Treatment of alcohol dependence): W: decision granting a waiver in all age groups for all conditions or indications, 17 Mar 2017Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA EMEA-001549-PIP02-14, 2026-11-11
- EU orphan designation: yes · EU/3/23/2846 positive 13 Oct 2023: Treatment of narcolepsy; EU/3/20/2386 positive 6 Jan 2021: Treatment of idiopathic hypersomnia; EU/3/02/131 withdrawn 3 Feb 2003: Treatment of narcolepsyRule: 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 · Xyrem: authorised since 13 Oct 2005Rule: 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 Xyrem, 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 sodium oxybate, baclofen, oxybate, arbaclofen, arbaclofen placarbil, lesogaberan, sgs-742Rule: 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 · 42 interventional studies of sodium oxybate, baclofen, oxybate, arbaclofen, arbaclofen placarbil, lesogaberan, sgs-742 include patients under 18; 4 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 7 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.