SLC12A3 solute carrier family 12 member 3
ENSG00000070915 · protein coding · Open Targets profile
Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules (PubMed:18270262, PubMed:21613606, PubMed:22009145, PubMed:36351028, PubMed:36792826). Also acts as a receptor for the pro-inflammatory cytokine IL18, thereby contributing to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2 (By similarity). May act either independently of IL18R1, or in a complex with IL18R1 (By similarity). {ECO:0000250|UniProtKB:P59158, ECO:0000269|PubMed:18270262, ECO:0000269|PubMed:21613606, ECO:0000269|PubMed:22009145, ECO:0000269|PubMed:36351028, ECO:0000269|PubMed:36792826}.
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 Withdrawn means the drug was pulled from the market or from development.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, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf, UniProt loc med conf, UniProt SigP or TMHMM
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination
gnomAD loss of function constraint: o/e 0.8593400120735168 (upper bound 1.0113999843597412). 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 121 registry trials, updated in the last three years, of the most advanced drugs against SLC12A3 (trichlormethiazide, chlorothiazide, benzthiazide, cyclothiazide, hydroflumethiazide, quinethazone, methyclothiazide, polythiazide, bendroflumethiazide, chlorthalidone, indapamide, metolazone), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Anthony RodgersThe George Institute · 2 of 2 trials Phase 2+
- Jeffrey TestaniYale University · 1 of 4 trials Phase 2+
- Seth W HolwerdaUniversity of Kansas Medical Center · 1 of 2 trials Phase 2+
- Adriana C FortiCentro de Estudos de Diabetes e Hipertensão · 1 of 1 trials Phase 2+
- Aharon AbboRambam Health Care Campus · 1 of 1 trials Phase 2+
- Alberto J Zamora Muciño-ArroyoInvestigación Biomédica para el Desarrollo de Fármacos S.A. de C.V. (BIOMED-AGS) · 1 of 1 trials Phase 2+
- Anand VaidyaBrigham and Women's Hospital, Harvard Medical School · 1 of 1 trials Phase 2+
- Areef IshaniMinneapolis VA Health Care System, Minneapolis, MN · 1 of 1 trials Phase 2+
- Benjamin BushUTMB · 1 of 1 trials Phase 2+
- Branko BraamUniversity of Alberta · 1 of 1 trials Phase 2+
- Bret GoodpasterTranslational Research Institute, Advent Health · 1 of 1 trials Phase 2+
- Cinthia L Patiño BernalCICMEX Centro de Investigación Clínica de México S. de R.L. de C.V. · 1 of 1 trials Phase 2+
- Craig AndersonThe George Institute · 1 of 1 trials Phase 2+
- Dalia A GomaaTanta University · 1 of 1 trials Phase 2+
- Daniel FusterDivision of Nephrology and Hypertension, Bern University Hospital, Bern, Switzerland · 1 of 1 trials Phase 2+
Registry trials of trichlormethiazide, chlorothiazide, benzthiazide, cyclothiazide, hydroflumethiazide, quinethazone, methyclothiazide, polythiazide, bendroflumethiazide, chlorthalidone, indapamide, metolazone 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; 95 of 103 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. 18 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
55 trials of drugs against SLC12A3 were stopped early; 6 give no reason
Terminated, withdrawn and suspended interventional trials of trichlormethiazide, chlorothiazide, benzthiazide, cyclothiazide, hydroflumethiazide, quinethazone, methyclothiazide, polythiazide, bendroflumethiazide, chlorthalidone, indapamide, metolazone, 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 55.
- terminated · 2026-07-14 · The University of Texas Medical Branch, Galveston · Hydrochlorothiazide 50mg Tablet“Futility of the study”
- terminated · 2026-05-08 · University of Alberta · Chlorthalidone“Personnel/staffing issues.”
- terminated · 2026-01-13 · University of California, San Francisco · Anti-hypertensive agent: Chlorthalidone“Funding limitations.”
- withdrawn · 2025-12-08 · EMS · Olmesartan Medoxomil 20mg + Chlorthalidone 12,5mg, Olmesartan 20mg + hydrochlorothiazide 12,5mg“Decided by Sponsor”
- withdrawn · 2025-12-08 · EMS · Olmesartan medoxomil 40mg + chlorthalidone 12,5mg, Olmesartan medoxomil 40mg + chlorthalidone 25mg, Olmesartan 40mg + Hydrochlorothiazide 12,5mg, Olmesartan 40mg + Hydrochlorothiazide 25mg“Decided by Sponsor”
- terminated · 2025-06-05 · Stanford University · Metolazone“Lack of resources”
- terminated · 2025-02-14 · Stadtspital Zürich · Metolazone“Low recruitment in both centers”
- terminated · 2024-07-29 · University of Iowa · Hydrochlorothiazide“Funding ended”
- terminated · 2024-02-28 · Penn State University · Hydrochlorothiazide“COVID shut down human subjects research and then the grant funding expired”
- terminated · 2023-10-24 · Novartis · Benazepril/hydrochlorothiazide 20/12.5 mg - Dose Level 1 from Day 1 to Month 1, Benazepril/hydrochlorothiazide 40/12.5 mg - Dose Level 2 from Month 1 to Month 2, Benazepril/hydrochlorothiazide 40/25 mg - Dose Level 3 from Month 2 to Month 3 and thereafter“The study was terminated early because of significant efficacy results for the primary endpoint in favor of benazepril/amlodipine treatment.”
- withdrawn · 2023-10-13 · Northwestern University · Chlorthalidone“Screened participants did not meet inclusion criteria prior to study completion date”
- withdrawn · 2023-05-03 · Ochsner Health System · Furosemide plus ChlorothiazideNo reason given
- terminated · 2023-04-14 · Gary L. Pierce · Hydrochlorothiazide“Funding expired”
- withdrawn · 2022-12-01 · Scripps Health · Metolazone“no participants enrolled”
- suspended · 2022-07-27 · EMS · Indapamide / Losartan“Substancial amendment”
- withdrawn · 2022-07-27 · EMS · Indapamide SR 1.5 MG“Sponsor decision”
- withdrawn · 2021-12-15 · University Hospital Tuebingen · Hydrochlorothiazide 25 mg“change in sponsor”
- withdrawn · 2021-12-09 · VA Office of Research and Development · matched by the registry's drug synonyms“The project has ended prior to beginning.”
- terminated · 2021-10-22 · University of Maryland, Baltimore · Metolazone 60 minutes prior to furosemide, Metolazone concurrently with furosemide“Insufficient rate of patient enrollment/accrual.”
- withdrawn · 2021-08-30 · Ramona Gelzer Bell · matched by the registry's drug synonyms“Due to low enrollment, COVID-19 pandemic causing suspension of most outpatient elective procedures, and no protected research time, Dr. Gelzer Bell is unable to continue this study.”
- terminated · 2021-05-25 · The George Institute · telmisartan 20 mg + amlodipine 2.5mg + indapamide 1.25mg“Not feasible to continue”
- terminated · 2021-04-01 · The George Institute · telmisartan 20mg + amlodipine 2.5mg +indapamide 1.25mg“Contractual and financial issues.”
- withdrawn · 2021-02-24 · EMS · matched by the registry's drug synonyms“The design of this protocol was rewritten due to regulatory recommendations.”
- terminated · 2021-02-16 · University of Virginia · Metolazone Oral Tablet, Chlorothiazide Injection“Low enrollment”
- withdrawn · 2021-02-04 · Cedars-Sinai Medical Center · matched by the registry's drug synonyms“Due to the Pandemic, we decided to end this study.”
Paediatric incentives and obligations for SLC12A3's drugs
For trichlormethiazide, chlorothiazide, benzthiazide, cyclothiazide, hydroflumethiazide, quinethazone, methyclothiazide, polythiazide, bendroflumethiazide, chlorthalidone, indapamide, metolazone: 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 · SLC12A3 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-003600-PIP01-24 (Indapamide;ramipril, Treatment of hypertension): W: decision granting a waiver in all age groups for all conditions or indications, 17 Jul 2024; EMEA-003498-PIP01-23 (ramipril;Indapamide, Treatment of hypertension): W: decision granting a waiver in all age groups for all conditions or indications, 1 Dec 2023; EMEA-003401-PIP01-23 (Candesartan cilexetil;Indapamide, Treatment of hypertension): W: decision granting a waiver in all age groups for all conditions or indications, 14 Jun 2023; EMEA-003372-PIP01-22 (ramipril;Indapamide, Treatment of hypertension): W: decision granting a waiver in all age groups for all conditions or indications, 12 May 2023; +18 moreRule: 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 trichlormethiazide, chlorothiazide, benzthiazide, cyclothiazide, hydroflumethiazide, quinethazone, methyclothiazide, polythiazide, bendroflumethiazide, chlorthalidone, indapamide, metolazoneRule: 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 trichlormethiazide, chlorothiazide, benzthiazide, cyclothiazide, hydroflumethiazide, quinethazone, methyclothiazide, polythiazide, bendroflumethiazide, chlorthalidone, indapamide, metolazoneRule: 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 trichlormethiazide, chlorothiazide, benzthiazide, cyclothiazide, hydroflumethiazide, quinethazone, methyclothiazide, polythiazide, bendroflumethiazide, chlorthalidone, indapamide, metolazoneRule: 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 · 19 interventional studies of trichlormethiazide, chlorothiazide, benzthiazide, cyclothiazide, hydroflumethiazide, quinethazone, methyclothiazide, polythiazide, bendroflumethiazide, chlorthalidone, indapamide, metolazone include patients under 18; 0 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 13 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.