CHRNB4 cholinergic receptor nicotinic beta 4 subunit
ENSG00000117971 · protein coding · Open Targets profile
Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate synaptic transmission in the nervous system and the neuromuscular junction. Each nAchR subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, cation permeability, and binding to allosteric modulators (PubMed:20881005, PubMed:31488329, PubMed:8663494, PubMed:8906617, PubMed:9203638). CHRNB4 forms heteropentameric neuronal acetylcholine receptors with CHRNA2, CHRNA3 and CHRNA4, as well as CHRNA5 and CHRNB3 as accesory subunits (PubMed:11118490, PubMed:20881005, PubMed:8663494). CHRNA3:CHRNB4 being predominant in neurons of the autonomic ganglia, it is known as ganglionic nicotinic receptor (PubMed:31488329). CHRNA3:CHRNB4 or CHRNA3:CHRNA5:CHRNB4 play also an important role in the habenulo- interpeduncular tract, modulating the mesolimbic dopamine system and affecting reward circuits and addiction (By similarity). Hypothalamic CHRNA3:CHRNB4 nAChR activation by nicotine leads to activation of POMC neurons and a decrease in food intake (By similarity). {ECO:0000250|UniProtKB:P12392, ECO:0000250|UniProtKB:Q8R493, ECO:0000269|PubMed:11118490, ECO:0000269|PubMed:20881005, ECO:0000269|PubMed:31488329, ECO:0000269|PubMed:8663494, ECO:0000269|PubMed:8906617, ECO:0000269|PubMed:9203638}.
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 Withdrawn means the drug was pulled from the market or from development.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
- Other modalities
- Advanced Clinical
gnomAD loss of function constraint: o/e 0.5698599815368652 (upper bound 0.8073599934577942). 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 12 registry trials, updated in the last three years, of the most advanced drugs against CHRNB4 (mecamylamine, pentolinium, trimethaphan, larazotide, simpinicline, ASM-024), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Satish R RajVanderbilt University School of Medicine · 1 of 1 trials Phase 2+
- Italo BiaggioniVanderbilt University · 0 of 3 trials Phase 2+
- Paul NewhouseVanderbilt University Medical Center · 0 of 2 trials Phase 2+
- Julie A DumasUniversity of Vermont · 0 of 1 trials Phase 2+
- Paul A NewhouseVanderbilt University · 0 of 1 trials Phase 2+
Registry trials of mecamylamine, pentolinium, trimethaphan, larazotide, simpinicline, ASM-024 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; 9 of 12 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. Source: ClinicalTrials.gov, fetched live.
9 trials of drugs against CHRNB4 were stopped early; 1 give no reason
Terminated, withdrawn and suspended interventional trials of mecamylamine, pentolinium, trimethaphan, larazotide, simpinicline, ASM-024, 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 9 most recent of 9.
- terminated · 2024-06-13 · Massachusetts General Hospital · Larazotide Acetate“Decline in MISC cases”
- terminated · 2024-01-09 · Vanderbilt University · Trimethaphan“We were not able to enroll adequate number of participants that met the inclusion/exclusion criteria, and we run out of funding.”
- terminated · 2022-07-26 · 9 Meters Biopharma, Inc. · Larazotide“Trial terminated by Sponsor”
- withdrawn · 2021-06-08 · Vanderbilt University Medical Center · Trimethaphan“The investigators decided not to perform the study. No participants have been enrolled.”
- terminated · 2018-10-03 · Amicus Therapeutics · matched by the registry's drug synonyms“The Sponsor (Amicus Therapeutics) terminated this study for logistical reasons.”
- terminated · 2018-10-02 · Amicus Therapeutics · matched by the registry's drug synonyms“Amicus Therapeutics discontinued Study AT1001-041 for logistical reasons.”
- terminated · 2015-02-10 · Asmacure Ltée · ASM-024“Lack of efficacy”
- terminated · 2012-11-20 · AstraZeneca · matched by the registry's drug synonymsNo reason given
- terminated · 2010-11-23 · CoMentis · Mecamylamine“Sponsor decision”
Paediatric incentives and obligations for CHRNB4's drugs
For mecamylamine, pentolinium, trimethaphan, larazotide, simpinicline, ASM-024: 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 · CHRNB4 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 mecamylamine, pentolinium, trimethaphan, larazotide, simpinicline, asm-024Rule: 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 mecamylamine, pentolinium, trimethaphan, larazotide, simpinicline, asm-024Rule: 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 mecamylamine, pentolinium, trimethaphan, larazotide, simpinicline, asm-024Rule: 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 mecamylamine, pentolinium, trimethaphan, larazotide, simpinicline, asm-024Rule: 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 · 9 interventional studies of mecamylamine, pentolinium, trimethaphan, larazotide, simpinicline, asm-024 include patients under 18; 1 is 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 8 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.