SLC6A2 solute carrier family 6 member 2
ENSG00000103546 · protein coding · Open Targets profile
Mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline), the primary signaling neurotransmitter in the autonomic sympathetic nervous system (PubMed:2008212, PubMed:8125921, PubMed:38750358). Is responsible for norepinephrine re-uptake and clearance from the synaptic cleft, thus playing a crucial role in norepinephrine inactivation and homeostasis (By similarity). Can also mediate sodium- and chloride-dependent transport of dopamine (PubMed:11093780, PubMed:8125921, PubMed:39395208, PubMed:39048818). {ECO:0000250|UniProtKB:O55192, ECO:0000269|PubMed:11093780, ECO:0000269|PubMed:2008212, ECO:0000269|PubMed:38750358, ECO:0000269|PubMed:39048818, ECO:0000269|PubMed:8125921}.
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 Withdrawn means the drug was pulled from the market or from development.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
- UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM
- PROTAC
- Small Molecule Binder
gnomAD loss of function constraint: o/e 0.3628700077533722 (upper bound 0.5034999847412109). 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 64 registry trials, updated in the last three years, of the most advanced drugs against SLC6A2 (benzphetamine, levomilnacipran, amoxapine, maprotiline, guanadrel, orphenadrine, nortriptyline, iobenguane i 131, viloxazine, dexmethylphenidate, milnacipran, trimipramine), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Ann ChildressPrincipal Investigator · 4 of 4 trials Phase 2+
- Jonathan RubinSupernus Pharmaceuticals, Inc. · 4 of 4 trials Phase 2+
- Matt BramsCingulate · 2 of 3 trials Phase 2+
- Gregory YanikUniversity of Michigan Rogel Cancer Center · 1 of 2 trials Phase 2+
- John M. MarisChildren's Hospital of Philadelphia · 1 of 2 trials Phase 2+
- Katherine K. MatthayUniversity of California, San Francisco · 1 of 2 trials Phase 2+
- Ad A.A.M MascleeMaastricht University Medical Center · 1 of 1 trials Phase 2+
- Andrea NackleyDuke University · 1 of 1 trials Phase 2+
- Andrew BisharaUCSF Department of Anesthesia · 1 of 1 trials Phase 2+
- Antoine LEMAIREHospital of Valenciennes · 1 of 1 trials Phase 2+
- Aristotle VoineskosCentre for Addiction and Mental Health · 1 of 1 trials Phase 2+
- Brian CallaghanUniversity of Michigan · 1 of 1 trials Phase 2+
- Carmen AndreescuAssistant Professor of Psychiatry · 1 of 1 trials Phase 2+
- Christopher DrakeInvestigator · 1 of 1 trials Phase 2+
- Darin B BrimhallPPD Phase I Clinic · 1 of 1 trials Phase 2+
Registry trials of benzphetamine, levomilnacipran, amoxapine, maprotiline, guanadrel, orphenadrine, nortriptyline, iobenguane i 131, viloxazine, dexmethylphenidate, milnacipran, trimipramine 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; 54 of 62 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. 2 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
32 trials of drugs against SLC6A2 were stopped early; 5 give no reason
Terminated, withdrawn and suspended interventional trials of benzphetamine, levomilnacipran, amoxapine, maprotiline, guanadrel, orphenadrine, nortriptyline, iobenguane i 131, viloxazine, dexmethylphenidate, milnacipran, trimipramine, 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 32.
- suspended · 2026-10-27 · University of California, Irvine · Nortriptyline“Enrollment temporarily paused pending IRB continuing review; recruitment expected to resume.”
- terminated · 2026-08-25 · The Cleveland Clinic · Nortriptyline“Not enough participants - only 5 since the study started”
- suspended · 2026-05-05 · Cingulate Therapeutics · CTx-1301 - Dexmethylphenidate 6.25mg, CTx-1301 - Dexmethylphenidate 12.5mg, CTx-1301 - Dexmethylphenidate 18.75mg, CTx-1301 - Dexmethylphenidate 25.0mg, CTx-1301 - Dexmethylphenidate 31.25mg, CTx-1301 - Dexmethylphenidate 37.5mg“Continuation of the study is not required for NDA submission via the 505(b)(2) pathway”
- terminated · 2025-09-10 · Lancaster General Hospital · Nortriptyline“The study was stopped prematurely due to a low enrollment rate.”
- terminated · 2025-09-02 · Gustave Roussy, Cancer Campus, Grand Paris · matched by the registry's drug synonyms“The Sponsor has been notified of an interruption in the international supply, and there is a possibility that 131I-mlBG would be unavailable to patients randomised to arm A of the trial”
- terminated · 2025-07-03 · Maastricht University Medical Center · Nortriptyline“The inclusion of participants went more difficult than initially thought. Preliminary analysis showed that the difference between the groups was great enough to draw conclusions from it, so the trial is terminated prematurely.”
- withdrawn · 2024-04-29 · David Bushnell · matched by the registry's drug synonyms“Azedra withdrawn from US market”
- withdrawn · 2022-08-22 · University of Rochester · Temozolomide, Tamoxifen, Maprotiline“One of the drugs for the study is not commercially available.”
- withdrawn · 2022-05-19 · AC Camargo Cancer Center · matched by the registry's drug synonyms“No participants enrolled”
- terminated · 2022-04-29 · Mansoura University · Orphenadrine“COVID 19 Pandemic”
- terminated · 2021-09-09 · Wake Forest University Health Sciences · matched by the registry's drug synonyms“low accrual; loss of funding”
- withdrawn · 2021-06-08 · Sue O'Dorisio · matched by the registry's drug synonyms“competing clinical trial opening”
- terminated · 2021-05-14 · Miguel Pampaloni · matched by the registry's drug synonyms“Funding”
- terminated · 2021-04-23 · St. Louis University · nortriptyline“Lack of enrollment”
- terminated · 2021-03-05 · Temple University · matched by the registry's drug synonyms“Futility; study coordinator left and were unable to continue data collection; missing data”
- terminated · 2020-09-03 · Columbia University · Milnacipran“Poor recruitment”
- terminated · 2020-06-01 · New York State Psychiatric Institute · Milnacipran and D-cycloserine“Slow recruitment due to strict inclusion/exclusion criteria”
- withdrawn · 2020-05-27 · Western Galilee Hospital-Nahariya · orphenadrine“inability to complete recruitment as planned”
- terminated · 2019-05-14 · Forest Laboratories · MilnacipranNo reason given
- terminated · 2018-02-28 · Hannover Medical School · Trimipramine, Nortriptyline, MaprotilineNo reason given
- withdrawn · 2017-04-25 · Sheppard Pratt Health System · matched by the registry's drug synonyms“unable to enroll subjects”
- terminated · 2017-04-13 · Spencer Dorn, MD, MPH · Milnacipran“Due to recruitment difficulties the study is terminated.”
- withdrawn · 2017-01-12 · Brigham and Women's Hospital · matched by the registry's drug synonyms“Company decided to discontinue”
- withdrawn · 2015-12-21 · University College, London · matched by the registry's drug synonyms“Poor patient accrual”
- withdrawn · 2015-11-26 · Molecular Insight Pharmaceuticals, Inc. · Ultratrace Iobenguane I 131No reason given
Paediatric incentives and obligations for SLC6A2's drugs
For benzphetamine, levomilnacipran, amoxapine, maprotiline, guanadrel, orphenadrine, nortriptyline, iobenguane i 131, viloxazine, dexmethylphenidate, milnacipran, trimipramine: 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 · SLC6A2 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-003337-PIP01-22 (diclofenac;orphenadrine (citrate), Treatment of pain): W: decision granting a waiver in all age groups for all conditions or indications, 31 Jan 2023; EMEA-001724-PIP01-14 (levomilnacipran, Treatment of stroke): RW: decision refers to a refusal on a request for waiver in all age groups for the listed condition(s), 5 Jun 2015Rule: 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 benzphetamine, levomilnacipran, amoxapine, maprotiline, guanadrel, orphenadrine, nortriptyline, iobenguane i 131, viloxazine, dexmethylphenidate, milnacipran, trimipramineRule: 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 · Impulsor: refused; Milnacipran Pierre Fabre Medicament: refusedRule: 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 benzphetamine, levomilnacipran, amoxapine, maprotiline, guanadrel, orphenadrine, nortriptyline, iobenguane i 131, viloxazine, dexmethylphenidate, milnacipran, trimipramineRule: 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 · 74 interventional studies of benzphetamine, levomilnacipran, amoxapine, maprotiline, guanadrel, orphenadrine, nortriptyline, iobenguane i 131, viloxazine, dexmethylphenidate, milnacipran, trimipramine include patients under 18; 14 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 104 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.