CHRNB2 cholinergic receptor nicotinic beta 2 subunit
ENSG00000160716 · 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:22361591, PubMed:27698419, PubMed:29720657, PubMed:38454578). CHRNB2 forms heteropentameric neuronal acetylcholine receptors with CHRNA2, CHRNA3, CHRNA4 and CHRNA6, as well as CHRNA5 and CHRNB3 as accesory subunits (PubMed:16835356, PubMed:20881005, PubMed:22361591, PubMed:27698419, PubMed:29720657, PubMed:38454578, PubMed:8663494). Found in two major stoichiometric forms,(CHRNA4)3:(CHRNB2)2 and (CHRNA4)2:(CHRNB2)3, the two stoichiometric forms differ in their unitary conductance, calcium permeability, ACh sensitivity and potentiation by divalent cation (PubMed:27698419, PubMed:29720657, PubMed:38454578). Heteropentameric channels with CHRNA6 and CHRNA4 exhibit high sensitivity to ACh and nicotine and are predominantly expressed in only a few brain areas, including dopaminergic neurons, norepirephrine neurons and cells of the visual system. nAChrs containing CHRNA6 subunits mediate endogenous cholinergic modulation of dopamine and gamma-aminobutyric acid (GABA) release in response to nicotine at nerve terminals (By similarity). Also forms functional nAChRs with other subunits such as CHRNA7:CHRNB2, mainly expressed in basal forebrain cholinergic neurons (PubMed:33239400, PubMed:38161283). {ECO:0000250|UniProtKB:P12390, ECO:0000269|PubMed:16835356, ECO:0000269|PubMed:20881005, ECO:0000269|PubMed:22361591, ECO:0000269|PubMed:27698419, ECO:0000269|PubMed:29720657, ECO:0000269|PubMed:33239400, ECO:0000269|PubMed:38161283, ECO:0000269|PubMed:38454578, ECO:0000269|PubMed:8663494}.
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 Withdrawn means the drug was pulled from the market or from development.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, High-Quality Pocket, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf, UniProt loc med conf, UniProt SigP or TMHMM
- PROTAC
- Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.7728800177574158 (upper bound 1.033400058746338). 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 400 registry trials, updated in the last three years, of the most advanced drugs against CHRNB2 (cytisinicline, varenicline, nicotine, dianicline, nicotine polacrilex, dexmecamylamine, simpinicline, sofinicline, ispronicline, AZD1446, CP-601927, pozanicline), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Andrew PipeOttawa Heart Institute Research Corporation · 3 of 3 trials Phase 2+
- Jason RobinsonM.D. Anderson Cancer Center · 2 of 3 trials Phase 2+
- E. Jennifer EdelmanYale University · 2 of 2 trials Phase 2+
- Megan E PiperUniversity of Wisconsin, Madison · 2 of 2 trials Phase 2+
- Megan PiperUW School of Medicine and Public Health · 2 of 2 trials Phase 2+
- Robert ReidOttawa Heart Institute Research Corporation · 2 of 2 trials Phase 2+
- Xianhui WangSan Diego State University · 2 of 2 trials Phase 2+
- Brittney L Keller-HamiltonOhio State University Comprehensive Cancer Center · 1 of 5 trials Phase 2+
- Michael BusinelleUniversity of Oklahoma Health Sciences · 1 of 3 trials Phase 2+
- Omar El-ShahawyNYU Langone Health · 1 of 3 trials Phase 2+
- Amanda PalmerMedical University of South Carolina · 1 of 2 trials Phase 2+
- Darla E. KendzorThe University of Oklahoma Health Campus · 1 of 2 trials Phase 2+
- Jamie OstroffMemorial Sloan Kettering Cancer Center · 1 of 2 trials Phase 2+
- Jan BlalockM.D. Anderson Cancer Center · 1 of 2 trials Phase 2+
- Jason D RobinsonM.D. Anderson Cancer Center · 1 of 2 trials Phase 2+
Registry trials of cytisinicline, varenicline, nicotine, dianicline, nicotine polacrilex, dexmecamylamine, simpinicline, sofinicline, ispronicline, AZD1446, CP-601927, pozanicline 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; 370 of 373 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. 27 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
204 trials of drugs against CHRNB2 were stopped early; 20 of the 200 most recent give no reason
Terminated, withdrawn and suspended interventional trials of cytisinicline, varenicline, nicotine, dianicline, nicotine polacrilex, dexmecamylamine, simpinicline, sofinicline, ispronicline, AZD1446, CP-601927, pozanicline, 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 204.
- terminated · 2026-11-06 · Yale University · Varenicline“recruitment challenges”
- terminated · 2026-10-26 · Washington University School of Medicine · matched by the registry's drug synonyms“Due to low recruitment”
- terminated · 2026-10-16 · Fred Hutchinson Cancer Center · matched by the registry's drug synonyms“Discontinuation of funding”
- withdrawn · 2026-10-09 · University of Missouri-Columbia · matched by the registry's drug synonyms“Funding”
- withdrawn · 2026-10-09 · University of Missouri-Columbia · matched by the registry's drug synonyms“Study was submitted in preparation of potential NIH application being funded. However, the study was not funded.”
- withdrawn · 2026-09-17 · ProofPilot · matched by the registry's drug synonyms“Organization lost funding”
- withdrawn · 2026-09-15 · Virginia Polytechnic Institute and State University · matched by the registry's drug synonyms“We submitted to the NIH to change our aim and not do this study, therefore this never started.”
- terminated · 2026-08-07 · Institut Cancerologie de l'Ouest · Nicotine Replacement Therapy (NRT)“lack of patient enrolment”
- withdrawn · 2026-07-07 · Mayo Clinic · Standard Varenicline Dosing (1 mg BID), Increased Varenicline Dosing (1mg TID)“Unable to recruit eligible participants.”
- withdrawn · 2026-05-14 · University of Catania · matched by the registry's drug synonyms“We worked on a new dedicated protocolol GENESIS study”
- withdrawn · 2026-05-14 · University of Catania · matched by the registry's drug synonyms“We started with a dedicated protocolol GENESIS RCT”
- withdrawn · 2026-05-07 · University of Oklahoma · matched by the registry's drug synonyms“Early termination of federal grant.”
- terminated · 2026-04-17 · Children's Hospital Los Angeles · matched by the registry's drug synonyms“This study has stopped its recruitment.”
- withdrawn · 2026-04-13 · Shenyang Sixth People's Hospital · matched by the registry's drug synonyms“needs major change in study protocol”
- terminated · 2026-04-08 · CMC Ambroise Paré · matched by the registry's drug synonyms“Risk-benefit analysis”
- terminated · 2026-02-27 · Luzerner Kantonsspital · matched by the registry's drug synonyms“The study is being terminated prematurely due to insufficient participant recruitment.”
- terminated · 2026-02-27 · National Institute on Drug Abuse (NIDA) · matched by the registry's drug synonyms“Administrative closure (PI unavailability)”
- terminated · 2026-02-27 · RAI Services Company · matched by the registry's drug synonyms“The study was terminated due to data integrity concerns that affected the ability to reliably assess the study endpoints.”
- withdrawn · 2026-02-13 · University of Minnesota · matched by the registry's drug synonyms“No longer funded and not moving forward”
- terminated · 2025-12-22 · Roswell Park Cancer Institute · matched by the registry's drug synonyms“End of grant”
- withdrawn · 2025-12-19 · RAND · matched by the registry's drug synonyms“NIA funded the first phase of the R21. The clinical trial never began as the R33 was not supported.”
- suspended · 2025-11-20 · National Cancer Institute (NCI) · matched by the registry's drug synonyms“Study on hold pending consideration for amendment.”
- terminated · 2025-09-09 · University of Miami · matched by the registry's drug synonyms“Recruitment for the study proved to be a significant challenge, raising important concerns about its overall feasibility.”
- suspended · 2025-07-11 · The University of Texas Health Science Center, Houston · matched by the registry's drug synonyms“We are hiring staff”
- terminated · 2025-06-24 · Third People's Hospital, Huzhou City, Zhejiang Province, China · matched by the registry's drug synonyms“the sponsor has determined that access to the full dataset is no longer available”
Paediatric incentives and obligations for CHRNB2's drugs
For cytisinicline, varenicline, nicotine, dianicline, nicotine polacrilex, dexmecamylamine, simpinicline, sofinicline, ispronicline, AZD1446, CP-601927, pozanicline: 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 · CHRNB2 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 cytisinicline, varenicline, nicotine, dianicline, nicotine polacrilex, dexmecamylamine, simpinicline, sofinicline, ispronicline, azd1446, cp-601927, pozaniclineRule: 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 cytisinicline, varenicline, nicotine, dianicline, nicotine polacrilex, dexmecamylamine, simpinicline, sofinicline, ispronicline, azd1446, cp-601927, pozaniclineRule: 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 · Champix: authorised since 25 Sept 2006Rule: 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 Champix, 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 cytisinicline, varenicline, nicotine, dianicline, nicotine polacrilex, dexmecamylamine, simpinicline, sofinicline, ispronicline, azd1446, cp-601927, pozaniclineRule: 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 · 217 interventional studies of cytisinicline, varenicline, nicotine, dianicline, nicotine polacrilex, dexmecamylamine, simpinicline, sofinicline, ispronicline, azd1446, cp-601927, pozanicline include patients under 18; 44 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 16 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.