Live from Open Targets Platform, fetched 2026-11-12 04:30 UTC. Every row links to its source record.

CLCN2 chloride voltage-gated channel 2

ENSG00000114859 · protein coding · Open Targets profile

Voltage-gated and osmosensitive chloride channel. Forms a homodimeric channel where each subunit has its own ion conduction pathway. Conducts double-barreled currents controlled by two types of gates, two fast glutamate gates that control each subunit independently and a slow common gate that opens and shuts off both subunits simultaneously. Displays inward rectification currents activated upon membrane hyperpolarization and extracellular hypotonicity (PubMed:16155254, PubMed:17567819, PubMed:19191339, PubMed:23632988, PubMed:29403011, PubMed:29403012, PubMed:36964785, PubMed:38345841). Contributes to chloride conductance involved in neuron excitability. In hippocampal neurons, generates a significant part of resting membrane conductance and provides an additional chloride efflux pathway to prevent chloride accumulation in dendrites upon GABA receptor activation. In glia, associates with the auxiliary subunit HEPACAM/GlialCAM at astrocytic processes and myelinated fiber tracts where it may regulate transcellular chloride flux buffering extracellular chloride and potassium concentrations (PubMed:19191339, PubMed:22405205, PubMed:23707145). Regulates aldosterone production in adrenal glands. The opening of CLCN2 channels at hyperpolarized membrane potentials in the glomerulosa causes cell membrane depolarization, activation of voltage-gated calcium channels and increased expression of aldosterone synthase, the rate-limiting enzyme for aldosterone biosynthesis (PubMed:29403011, PubMed:29403012). Contributes to chloride conductance in retinal pigment epithelium involved in phagocytosis of shed photoreceptor outer segments and photoreceptor renewal (PubMed:36964785). Conducts chloride currents at the basolateral membrane of epithelial cells with a role in chloride reabsorption rather than secretion (By similarity) (PubMed:16155254). Permeable to small monovalent anions with chloride > thiocyanate > bromide > nitrate > iodide ion selectivity (By similarity) (PubMed:29403012). {ECO:0000250|UniProtKB:P35525, ECO:0000250|UniProtKB:Q9R0A1, ECO:0000269|PubMed:16155254, ECO:0000269|PubMed:17567819, ECO:0000269|PubMed:19191339, ECO:0000269|PubMed:22405205, ECO:0000269|PubMed:23632988, ECO:0000269|PubMed:23707145, ECO:0000269|PubMed:29403011, ECO:0000269|PubMed:29403012, ECO:0000269|PubMed:36964785, ECO:0000269|PubMed:38345841}.

1 of the 2 drugs recorded against CLCN2 is approved

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.

In 1 of 6 cancers, the evidence for CLCN2 comes mainly from inherited variants

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.

Inherited (germline) variantsMutations in tumours (somatic)

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, Druggable Family
Antibody: UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM
PROTAC: Database Ubiquitination

gnomAD loss of function constraint: o/e 0.6646299958229065 (upper bound 0.8086199760437012). 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 4 registry trials, updated in the last three years, of the most advanced drugs against CLCN2 (lubiprostone, cobiprostone), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.

asmaa abdelnaby mohamed soliman
assistant lecturer · 1 of 1 trials Phase 2+
Ph1/Ph2NCT06543979 · Anorectal Manometery in Pediatric Chronic Refractory Constipation brief
Weidong Tong
Army Medical Center (Daping Hospital) · 1 of 1 trials Phase 2+
Ph3NCT07277907 · Efficacy and Safety of Lubiprostone in the Treatment of Slow Transit Constipation brief

2 of 3 trials of drugs against CLCN2 have sites only in countries outside the US, China, Europe and Japan

Registry trials of lubiprostone, cobiprostone 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; 3 of 3 have all sites in one country.

Sites only in this groupSites here and elsewhere

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. 1 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.

6 trials of drugs against CLCN2 were stopped early; 3 give no reason

Terminated, withdrawn and suspended interventional trials of lubiprostone, cobiprostone, 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 6 most recent of 6.

Ph4NCT01096290 brief why it stopped
terminated · 2020-11-20 · University of South Alabama · lubiprostone
“Number of needed participants could not be obtained”
Ph2NCT02544152 brief why it stopped
terminated · 2019-12-27 · Sucampo Pharma Americas, LLC · Lubiprostone
No reason given
Ph2NCT02542215 brief why it stopped
terminated · 2019-12-02 · Sucampo Pharma Americas, LLC · Cobiprostone
No reason given
Ph2NCT00737594 brief why it stopped
terminated · 2019-11-18 · Sucampo Pharma Americas, LLC · Cobiprostone
“Failure to enroll a suitable number of qualified subjects.”
N/ANCT00669461 brief why it stopped
terminated · 2016-12-30 · University of Arkansas · Lubiprostone
“Lack of recruitment”
N/ANCT00689026 brief why it stopped
terminated · 2014-10-20 · Augusta University · Lubiprostone
No reason given

Paediatric incentives and obligations for CLCN2's drugs

For lubiprostone, cobiprostone: 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 · CLCN2 is not on the list
Rule: 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-000245-PIP01-08-M06 (Lubiprostone, Treatment of constipation): PM: decision on the application for modification of an agreed PIP, 4 Nov 2019; compliance positive 28 Feb 2020
Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA EMEA-000245-PIP01-08-M06, 2026-11-11
EU orphan designation: no · No EU orphan designation names lubiprostone, cobiprostone
Rule: 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 lubiprostone, cobiprostone
Rule: 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 link
Rule: 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 lubiprostone, cobiprostone
Rule: 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 · 6 interventional studies of lubiprostone, cobiprostone include patients under 18; 0 are recruiting, not yet recruiting or active
Rule: 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 2 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
LUBIPROSTONE	Small molecule	phase 4	constipation disorder, irritable bowel syndrome, Chronic pain, bowel dysfunction, non-alcoholic fatty liver, Chronic constipation, HIV infectious disease, Parkinson disease	Open Targets · ChEMBL
COBIPROSTONE	Small molecule	phase 2	portal hypertension	Open Targets · ChEMBL