HRH2 histamine receptor H2
ENSG00000113749 · protein coding · Open Targets profile
G protein-coupled receptor for histamine, primarily mediating gastric acid secretion. Predominantly expressed in the gastric mucosa, couples to G(s) G alpha proteins upon histamine binding, leading to activation of adenylate cyclase and increased intracellular cyclic AMP (cAMP) levels (PubMed:38647423, PubMed:39333117). This signaling cascade stimulates parietal cells to secrete hydrochloric acid, playing a key role in digestive physiology. Also expressed in other tissues, including the heart and central nervous system, where it may contribute to cardiac stimulation and modulate neurotransmitter release (By similarity). {ECO:0000250|UniProtKB:P97292, ECO:0000269|PubMed:38647423, ECO:0000269|PubMed:39333117}.
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 Withdrawn means the drug was pulled from the market or from development.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
- GO CC high conf, UniProt loc med conf, UniProt SigP or TMHMM
- PROTAC
- Small Molecule Binder
gnomAD loss of function constraint: o/e 0.1987999975681305 (upper bound 0.45493999123573303). 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 HRH2 (betazole, nizatidine, tolazoline, ranitidine, methantheline, lafutidine, cimetidine, ranitidine bismuth, famotidine), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Brian A RobertsLeidos, Inc. · 2 of 2 trials Phase 2+
- Yafen LiangThe University of Texas Health Science Center, Houston · 2 of 2 trials Phase 2+
- Alberto PappoSt. Jude Children's Research Hospital · 1 of 1 trials Phase 2+
- Amy K DickeyMassachusetts General Hospital · 1 of 1 trials Phase 2+
- Beth HelminkM.D. Anderson Cancer Center · 1 of 1 trials Phase 2+
- Brian BadgwellM.D. Anderson Cancer Center · 1 of 1 trials Phase 2+
- Celeste FinnertyUniversity of Texas Medical Branch, Galveston · 1 of 1 trials Phase 2+
- David BernsteinUniversity of Cincinnati · 1 of 1 trials Phase 2+
- Derek W RussellUniversity of Alabama at Birmingham Heersink School of Medicine · 1 of 1 trials Phase 2+
- Everett VokesUniversity of Chicago · 1 of 1 trials Phase 2+
- Faisal Fa'akWashington University School of Medicine · 1 of 1 trials Phase 2+
- Farid EL HAJBICentre Oscar Lambret · 1 of 1 trials Phase 2+
- Gulab Fatima RaniInstitute of Pathology and Diagnostic Medicine, Khyber Medical University, Peshawar · 1 of 1 trials Phase 2+
- John H. StoneMassachusetts General Hospital · 1 of 1 trials Phase 2+
- Joseph RimandoEmory University Hospital/Winship Cancer Institute · 1 of 1 trials Phase 2+
Registry trials of betazole, nizatidine, tolazoline, ranitidine, methantheline, lafutidine, cimetidine, ranitidine bismuth, famotidine 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; 103 of 111 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. 9 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
50 trials of drugs against HRH2 were stopped early; 2 give no reason
Terminated, withdrawn and suspended interventional trials of betazole, nizatidine, tolazoline, ranitidine, methantheline, lafutidine, cimetidine, ranitidine bismuth, famotidine, methantheline bromide, 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 50.
- withdrawn · 2026-09-04 · University of Cincinnati · matched by the registry's drug synonyms“no funding for clinical research space”
- terminated · 2026-08-04 · Genzyme, a Sanofi Company · Ranitidine“Enrolment formally closed earlier than planned due to recruitment challenges.”
- terminated · 2026-06-23 · HonorHealth Research Institute · matched by the registry's drug synonyms“The study was terminated early per the recommendation of the Data and Safety Monitoring Board (DSMB) after a planned interim analysis met pre-specified criteria for futility.”
- terminated · 2026-03-18 · Centre Oscar Lambret · matched by the registry's drug synonyms“This decision was taken on June 20 2022 due to low recruitment over the past 4 years.”
- terminated · 2026-02-05 · National Institute of Allergy and Infectious Diseases (NIAID) · famotidine“The study was terminated early based on disease flare/lack of efficacy in the early phase of the trial.”
- terminated · 2025-12-02 · National Cancer Institute (NCI) · Famotidine“Site plans to become a site for a multicenter study of this therapy”
- terminated · 2025-11-21 · Restor3D · matched by the registry's drug synonyms“Decision of investigational team”
- terminated · 2025-09-17 · Sanofi · Ranitidine or equivalent“Terminated due to non-safety reasons”
- terminated · 2025-07-20 · Reema Padia · Famotidine“Slow recruitment due to few eligible patients”
- terminated · 2025-07-17 · Emory University · Famotidine, Famotidine Placebo“Study was terminated due to lack of funding.”
- withdrawn · 2025-06-03 · University of Miami · Famotidine“Study drug was not compliant with research pharmacy”
- terminated · 2025-02-06 · Bristol-Myers Squibb · Famotidine“Business objectives have changed”
- withdrawn · 2024-10-24 · Stephen Ruedrich · matched by the registry's drug synonyms“Not funded”
- withdrawn · 2024-08-13 · University of California, Los Angeles · matched by the registry's drug synonyms“Investigator decision”
- terminated · 2024-07-09 · Leidos Life Sciences · Famotidine“Low recruitment”
- terminated · 2024-04-16 · Ultragenyx Pharmaceutical Inc · matched by the registry's drug synonyms“Sponsor decision not related to safety concerns”
- terminated · 2024-02-02 · National Cancer Institute (NCI) · Famotidine“Study was closed early due to slow accrual.”
- 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.”
- terminated · 2023-12-01 · NYU College of Dentistry · matched by the registry's drug synonyms“Original PI who is no longer at the institution, the sponsor of this research study, Zimmer Biomet, along with the current PI have decided to close enrollment to the study and to early terminate the study.”
- withdrawn · 2023-10-10 · Leidos Life Sciences · Famotidine“COVID environment, lack of site confidence to enroll subjects, sites not suited to study procedures, decline of potential inpatient subjects at site”
- terminated · 2023-06-22 · Emory University · matched by the registry's drug synonyms“Loss of surgery team member deemed the study procedures impossible to achieve, and no replacement could be found in a timely manner to complete trial as initially planned.”
- terminated · 2023-03-03 · Hvidovre University Hospital · matched by the registry's drug synonyms“High early failure rates and adverse reactions in similar devices”
- terminated · 2022-12-20 · Mayo Clinic · Famotidine“low enrollment”
- terminated · 2022-09-30 · Profact, Inc. · Famotidine“Unable to recruit participants due to decline in COVID-19.”
- terminated · 2022-04-26 · Universitas Indonesia · matched by the registry's drug synonyms“Aerosol risk of COVID-19 spread resulting a slow subject recruitment”
Paediatric incentives and obligations for HRH2's drugs
For betazole, nizatidine, tolazoline, ranitidine, methantheline, lafutidine, cimetidine, ranitidine bismuth, famotidine, methantheline bromide: 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 · HRH2 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-000616-PIP01-09 (Ibuprofen;Famotidine, Chronic pain due to arthropathies): W: decision granting a waiver in all age groups for all conditions or indications, 9 Oct 2009Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA EMEA-000616-PIP01-09, 2026-11-11
- EU orphan designation: no · No EU orphan designation names betazole, nizatidine, tolazoline, ranitidine, methantheline, lafutidine, cimetidine, ranitidine bismuth, famotidine, methantheline bromideRule: 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: no · EMA lists no centrally authorised medicine of betazole, nizatidine, tolazoline, ranitidine, methantheline, lafutidine, cimetidine, ranitidine bismuth, famotidine, methantheline bromideRule: 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 betazole, nizatidine, tolazoline, ranitidine, methantheline, lafutidine, cimetidine, ranitidine bismuth, famotidine, methantheline bromideRule: 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 · 37 interventional studies of betazole, nizatidine, tolazoline, ranitidine, methantheline, lafutidine, cimetidine, ranitidine bismuth, famotidine, methantheline bromide include patients under 18; 7 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 12 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.