HRH4 histamine receptor H4
ENSG00000134489 · protein coding · Open Targets profile
G protein-coupled receptor primarily expressed in immune cells such as mast cells, eosinophils, basophils, dendritic cells and neutrophils that plays a key role in immune and inflammatory responses (PubMed:26948974). Mediates chemotaxis of immune cells to sites of inflammation or injury by responding to histamine (PubMed:26948974). Activation by histamine also influences the release of proinflammatory cytokines such as TNF, CCL4, IL6 and IFN-gamma (PubMed:29600327, PubMed:31583075). Ligand binding induces a conformation change that triggers signaling via G(i)/GNAI1 leading to decreased intracellular cAMP levels by inhibiting adenylate cyclase activity (PubMed:39333117). In addition, plays a role in the control of renal reabsorption processes, particularly albumin uptake (By similarity). {ECO:0000250|UniProtKB:Q91ZY2, ECO:0000269|PubMed:12503632, ECO:0000269|PubMed:26948974, ECO:0000269|PubMed:29600327, ECO:0000269|PubMed:31583075, 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 Withdrawn means the drug was pulled from the market or from development.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
- Advanced Clinical, 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 1.1547000408172607 (upper bound 1.87090003490448). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
No named investigators on registry trials of HRH4's approved or late-stage drugs in the last three years.
No terminated, withdrawn or suspended trials of HRH4's drugs are registered
Paediatric incentives and obligations for HRH4's drugs
For adriforant, UR-63325, toreforant: 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 · HRH4 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: no · No EMA paediatric investigation plan decision names adriforant, ur-63325, toreforantRule: 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 adriforant, ur-63325, toreforantRule: 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 adriforant, ur-63325, toreforantRule: 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 adriforant, ur-63325, toreforantRule: 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: no · No interventional study of adriforant, ur-63325, toreforant includes patients under 18Rule: 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 3 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.
| Drug | Type | Highest stage | Indications | Source records |
|---|---|---|---|---|
| ADRIFORANT | Small molecule | phase 2 | atopic eczema, psoriasis vulgaris, psoriasis, asthma, dermatitis | Open Targets · ChEMBL |
| UR-63325 | Small molecule | phase 2 | allergic rhinitis | Open Targets · ChEMBL |
| TOREFORANT | Small molecule | phase 2 | psoriasis vulgaris, rheumatoid arthritis, asthma | Open Targets · ChEMBL |