SLC12A1 solute carrier family 12 member 1
ENSG00000074803 · protein coding · Open Targets profile
Renal sodium, potassium and chloride non-electrogenic ion symporter that mediates the transepithelial NaCl reabsorption in the thick ascending limb and plays an essential role in the urinary concentration and volume regulation (PubMed:21321328). It can substitute NH4(+) for K(+), enabling NH4(+) apical transmembrane transport in the medullary thick ascending limb (MTAL). This function is crucial for maintaining ammonium homeostasis by the kidney, particularly during metabolic acidosis (By similarity). .
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 Withdrawn means the drug was pulled from the market or from development.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, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM
gnomAD loss of function constraint: o/e 0.682669997215271 (upper bound 0.8142300248146057). 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 169 registry trials, updated in the last three years, of the most advanced drugs against SLC12A1 (ethacrynic acid, ethacrynate, torsemide, bumetanide, furosemide), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Salim ShahSarfez Pharmaceuticals, Inc. · 4 of 4 trials Phase 2+
- Jonathan AbeleUniversity of Alberta · 2 of 2 trials Phase 2+
- Peter S PangIndiana University · 2 of 2 trials Phase 2+
- Mark PetrieUniversity of Glasgow · 1 of 2 trials Phase 2+
- Aharon AbboRambam Health Care Campus · 1 of 1 trials Phase 2+
- Alain MinaNational Cancer Institute (NCI) · 1 of 1 trials Phase 2+
- Alvin ChandraUniversity of Texas Southwestern Medical Center · 1 of 1 trials Phase 2+
- Ambarish PandeyUniversity of Texas Southwestern Medical Center · 1 of 1 trials Phase 2+
- Anas BizantiLakeland Regional Hospital · 1 of 1 trials Phase 2+
- Andrew LurieLakeland Regional Hospital · 1 of 1 trials Phase 2+
- Anna Maria Hibbs1. Rainbow Babies and Children's Hospital · 1 of 1 trials Phase 2+
- Annet KiraboVanderbilt University Medical Center · 1 of 1 trials Phase 2+
- Ashten B WaksUniversity of California, Irvine · 1 of 1 trials Phase 2+
- Bambang WidyantoroNational Cardiovascular Center Harapan Kita · 1 of 1 trials Phase 2+
- Bo LøfgrenDepartment of Medicine, Randers Regional Hospital · 1 of 1 trials Phase 2+
Registry trials of ethacrynic acid, ethacrynate, torsemide, bumetanide, furosemide 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; 154 of 160 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.
78 trials of drugs against SLC12A1 were stopped early; 9 give no reason
Terminated, withdrawn and suspended interventional trials of ethacrynic acid, ethacrynate, torsemide, bumetanide, furosemide, 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 78.
- withdrawn · 2026-09-28 · Sarfez Pharmaceuticals, Inc. · Extended Release Torsemide Tablets, Immedate Release Torsemide Tablets“No participants enrolled”
- withdrawn · 2026-09-22 · Sarfez Pharmaceuticals, Inc. · Combination Product: FDC of spironolactone and ER torsemide“No recruitment”
- withdrawn · 2026-06-09 · University Hospital, Limoges · Bumetanide“the recently feasibility study shows that the number of patients is insufficient in the centers”
- terminated · 2026-05-08 · University of Alberta · Furosemide“Personnel/staffing issues.”
- withdrawn · 2026-04-27 · Sarfez Pharmaceuticals, Inc. · torsemide“Recruitment issues”
- withdrawn · 2026-04-27 · Sarfez Pharmaceuticals, Inc. · Immediate release torsemide 20mg tablet, Extended release torsemide 24mg tablet“Recruitment issues.”
- terminated · 2026-04-24 · Sarfez Pharmaceuticals, Inc. · CHF Patients: ER Torsemide 40 mg, CHF Patients: Furosemide 40 mg“recruitment issues”
- withdrawn · 2026-01-29 · Prisma Health-Upstate · Bumetanide, intranasal 4mg“Change in Sponsor”
- terminated · 2025-09-16 · Rush University Medical Center · Furosemide Injection“The study halted prematurely due to staffing.”
- suspended · 2025-05-14 · Sclnow Biotechnology Co., Ltd. · matched by the registry's drug synonyms“Others”
- terminated · 2025-02-20 · Damascus University · Digoxin+furosemide+captopril“lack of necessary equipment”
- withdrawn · 2025-02-20 · Jan Kochanowski University · Furosemide Pill 150% equivalent iv dose, Furosemide Pill 200% equivalent iv dose, Furosemide Injection“no recruitment”
- terminated · 2025-02-14 · Stadtspital Zürich · Furosemide“Low recruitment in both centers”
- terminated · 2025-01-14 · University Hospital Tuebingen · Furosemide“Low recruiting rate and decision to evaluate as pilot study”
- terminated · 2024-11-21 · The George Institute · matched by the registry's drug synonyms“Difficulties in recruitment at both sites.”
- terminated · 2024-08-20 · Indiana University · matched by the registry's drug synonyms“COVID-19 pandemic. Initially had planned to resume study, but ultimately decided to close.”
- terminated · 2024-07-25 · Institut de Recherches Internationales Servier · Bumetanide Oral Solution“The 6-month efficacy analysis did not show any significant difference between bumetanide versus placebo in the treatment of ASD in the overall studied population. No unexpected safety concerns were identified.”
- terminated · 2024-01-11 · University of New Mexico · BumetanideNo reason given
- terminated · 2023-12-11 · Dr. John Muscedere · Nebulized Furosemide“Lack of recruitment due to decline in critically ill Covid-19 patients”
- terminated · 2023-10-23 · Wright State University · furosemide“Challenges with enrollment; primary investigator left the institution”
- terminated · 2023-08-30 · Thomas Jefferson University · Furosemide“The study was terminated prematurely due to low enrollment numbers and the development of better drugs to treat polyps (ie. Biologics) which were not available when the study began.”
- terminated · 2023-08-29 · Nuwellis, Inc. · matched by the registry's drug synonyms“Closed due to patient recruitment challenges. No interim analyses were completed; study closure was not related to any concerns about safety or futility.”
- terminated · 2023-06-05 · Institut de Recherches Internationales Servier · BUMETANIDE (S95008) for week 0 - 26, Open-Label BUMETANIDE (S95008) for weeks 26 - 52“The 6-month efficacy analysis did not show any significant difference between bumetanide versus placebo in the treatment of ASD in the overall studied population. No unexpected safety concerns were identified.”
- terminated · 2023-05-12 · University of California, San Francisco · Furosemide“Inadequate recruitment”
- withdrawn · 2023-05-11 · Indiana University · FurosemideNo reason given
Paediatric incentives and obligations for SLC12A1's drugs
For ethacrynic acid, ethacrynate, torsemide, bumetanide, furosemide: 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 · SLC12A1 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-003316-PIP01-22 (furosemide, Treatment of fluid retention): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 9 Aug 2023; EMEA-003065-PIP01-21 (eplerenone;furosemide, Treatment of heart failure): W: decision granting a waiver in all age groups for all conditions or indications, 3 Dec 2021; EMEA-001303-PIP01-12-M04 (bumetanide, Treatment of autism spectrum disorder): PM: decision on the application for modification of an agreed PIP, 9 Aug 2021; EMEA-000982-PIP01-10 (furosemide, Treatment of fluid retention): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 21 Oct 2011Rule: 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 ethacrynic acid, ethacrynate, torsemide, bumetanide, furosemideRule: 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 · Bopediat: authorised since 29 May 2026Rule: 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 Bopediat, 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 ethacrynic acid, ethacrynate, torsemide, bumetanide, furosemideRule: 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: yes · 47 interventional studies of ethacrynic acid, ethacrynate, torsemide, bumetanide, furosemide include patients under 18; 5 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, 2026-11-11
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 5 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.