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Protein / target

Solute carrier family 22 member 6

Encoded bySLC22A6Q4U2R8Homo sapiensSwiss-Prot
UniProt: Q4U2R8Ensembl: ENSG00000197901HGNC: HGNC:10970NCBI Gene: 9356
Clinically validated
Therapeutic maturity
1
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Alpha-ketoglutarate transmembrane transporter

Strongest disease association

Gout

Via encoding gene SLC22A6 · Clinical evidence · score 0.53

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate.

View complete UniProt function annotation

Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651)

Subcellular location

Basolateral cell membraneBasal cell membrane
Domains and Gene Ontology detail (20)

Gene Ontology

  • Cbasal plasma membrane
  • Cbasolateral plasma membrane
  • Ccaveola
  • Cextracellular exosome
  • Cplasma membrane
  • Cprotein-containing complex
  • Falpha-ketoglutarate transmembrane transporter activity
  • Fantiporter activity
  • Fprostaglandin transmembrane transporter activity
  • Fsecondary active transmembrane transporter activity
  • Fsolute:inorganic anion antiporter activity
  • Ftransmembrane transporter activity

563 aa · 62 kDa · 4 isoforms

Approved medicines with mapped indications

1 medicine · 1 area

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Gout1 medicine
probenecid

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

1

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

probenecid
Narrow target profileApprovedInhibitor

Solute carrier family 22 member 6 inhibitor

Indicated for Gout

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene SLC22A6

Gene-level evidence surfaced through the gene SLC22A6 that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Gout
0.66Moderately supported

Clinical evidence dominant · Open Targets 0.53

Autoimmune disorder of central nervous system
0.15Preliminary

Pathway evidence dominant · Open Targets 0.23 · no direct causal or clinical evidence

Kidney Failure, Chronic
0.13Preliminary

Literature evidence dominant · Open Targets 0.09 · no direct causal or clinical evidence

View evidence synthesis (3)
GoutModerately supported
0.66
agreement 0.50–0.81
Clinical97%Literature3%

Open Targets aggregate 0.53 · 2 independent evidence families

Autoimmune disorder of central nervous systemPreliminary
0.15
agreement 0.00–0.38
Pathway100%

Open Targets aggregate 0.23 · 1 independent evidence family · no direct causal or clinical evidence

Kidney Failure, ChronicPreliminary
0.13
agreement 0.00–0.32
Literature89%RNA expression11%

Open Targets aggregate 0.09 · 2 independent evidence families · no direct causal or clinical evidence

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Gout0.53
Autoimmune disorder of central nervous system0.23
Kidney Failure, Chronic0.09

Drug development

2 compounds recorded · 1 approved · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (2)
PROBENECIDApproval
PRATOSARTANPhase 3

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Approved Drug and High-Quality Ligand support this modality.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (database ubiquitination and small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · Approved DrugSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

Decrease, Population growth rateAOP-WikiIncreased MortalityAOP-Wiki

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

Probenecid, Pannexin 1 Channels for Alcohol Use DisorderPHASE2

RECRUITING · via probenecid · NCT07118618

Efficacy of Probenecid on Cluster Seizures During Anti Seizure Medication Withdrawal in Presurgical Focal Epilepsy Video-EEG MonitoringPHASE2

NOT_YET_RECRUITING · via probenecid · NCT07318870

Novel Use of Probenecid to Alleviate Symptoms of Opioid Withdrawal in People With Chronic Pain Undergoing Voluntary Opioid Tapering: a Pilot StudyPHASE2

RECRUITING · via probenecid · NCT04939623

An Open-label, Phase 1 Study to Individually Characterize the Food Effect, the Drug-Drug Interaction Effect of OAT Inhibition, and the Drug-Drug Interaction Effect of P-glycoprotein Inhibition on the Pharmacokinetics of MK-8527 in Healthy Adult ParticipantsPHASE1

ACTIVE_NOT_RECRUITING · via probenecid · NCT07661108

View all trials (26)
TRPV2 Agonists in Fontan Circulation PatientsPHASE4

COMPLETED · via probenecid · NCT03965351

Oseltamivir (Tamiflu) Dosing Strategies for Use During Influenza Prophylaxis (VA01)PHASE4

COMPLETED · via probenecid · NCT00304434

Ganciclovir-Cidofovir CMV Retinitis Trial (GCCRT)PHASE4

COMPLETED · via probenecid · NCT00000894

Treatment of Veterans With Heart Failure With Reduced Ejection Fraction With ProbenecidPHASE2/PHASE3

COMPLETED · via probenecid · NCT04551222

Modifiable Effectors of Renin System Activation: Treatment Evaluation (MODERATE)PHASE3

COMPLETED · via probenecid · NCT01320722

Addition of Probenecid to Penicillin-V Therapy: an Open Label, Cross-over Study in Healthy VolunteersPHASE1/PHASE2

COMPLETED · via probenecid · NCT05082909

Primary Prevention of Hypertension in Obese AdolescentsPHASE2

COMPLETED · via probenecid · NCT00288158

A Phase II/III Study of the Safety and Efficacy of 1-(S)-(3-Hydroxy-2-Phosphonylmethoxypropyl)Cytosine Dihydrate (Cidofovir; HPMPC) for the Treatment of Peripheral Cytomegalovirus Retinitis in Patients With AIDSPHASE2

COMPLETED · via probenecid · NCT00002437

AN INTERVENTIONAL, PHASE 1, OPEN-LABEL, TWO-COHORT, TWO-PERIOD, FIXED SEQUENCE STUDY TO ESTIMATE THE EFFECT OF MULTIPLE DOSES OF ITRACONAZOLE AND PROBENECID ON THE PHARMACOKINETICS OF SINGLE DOSE PF-07220060 ADMINISTERED UNDER THE FED CONDITION TO HEALTHY PARTICIPANTSPHASE1

COMPLETED · via probenecid · NCT07160738

Relative Bioavailability of Two Different BI 690517 Formulations as Well as the Effect of Multiple Doses of Probenecid on the Single Dose Pharmacokinetics of BI 690517 Following Oral Administration in Healthy Male and Female Subjects (a Randomised, Open-label, Three-way Crossover Trial)PHASE1

COMPLETED · via probenecid · NCT06647810

A Single Dose Oral Bioavailability Study of PanCytoVir™ Oral Suspension (100 mg/ml) 1000 mg Versus Probenecid 500 mg Tablets, 1000 mg (2 X 500 mg) in Healthy, Adult, Human Subjects Under Fasting ConditionsPHASE1

COMPLETED · via probenecid · NCT06025344

An Open-Label Study to Assess the Effect of Povorcitinib on Digoxin, Rosuvastatin, and Metformin Pharmacokinetics and the Effect of Probenecid on Povorcitinib Pharmacokinetics When Administered Orally to Healthy Adult ParticipantsPHASE1

COMPLETED · via probenecid · NCT06416800

A Open-Label, Two-sequence Phase I Drug-drug Interaction Clinical Study to Investigate the Pharmacokinetics of ZSP1273 With Digoxin, Rosuvastatin,Itraconazole and Probenecid in Healthy ParticipantsPHASE1

COMPLETED · via probenecid · NCT05954624

Pharmacokinetic Drug-Drug Interaction Study to Identify Biomarkers of Kidney TransportersEARLY_PHASE1

COMPLETED · via probenecid · NCT05365451

A Study In Healthy Subjects To Assess The Effects Of Rifampicin Capsules and Probenecid Tablets On The Pharmacokinetic Profile Of Rongliflozin CapsulesPHASE1

COMPLETED · via probenecid · NCT05497674

An Open-label, Drug Interaction Study to Evaluate Safety, Pharmacokinetic, and Pharmacodynamic Effect of Oral Administration of AV-101 Alone and in Combination With Probenecid in Healthy SubjectsPHASE1

UNKNOWN · via probenecid · NCT05280054

A Three-part, Single-center, Open-label, Phase I Clinical Study to Evaluate the Drug-drug Interactions (DDIs) Between DBPR108 and Warfarin Sodium/Digoxin/Probenecid in Healthy SubjectsPHASE1

COMPLETED · via probenecid · NCT05045313

A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE STUDY TO ASSESS SINGLE DOSE AND MULTIPLE DOSE PHARMACOKINETICS OF PF-04965842 AND ITS METABOLITES, AND THE EFFECT OF REPEAT-DOSE PROBENECID ON THE SINGLE DOSE PHARMACOKINETICS OF PF-04965842 AND ITS METABOLITES IN HEALTHY PARTICIPANTSPHASE1

COMPLETED · via probenecid · NCT03937258

A Phase 1, Two-Part, Open-label Study in Healthy Adult Volunteers to Assess a Single Dose of Vadadustat as a Victim in Drug-Drug Interactions With Cyclosporine, Probenecid and RifampinPHASE1

COMPLETED · via probenecid · NCT03801746

A Trial Investigating the Effect of Probenecid and Ciclosporin on the Pharmacokinetics of SNAC in Healthy SubjectsPHASE1

COMPLETED · via probenecid · NCT03466567

The Effect of Potent Inhibitors of Drug Transporters (Verapamil, Rifampin, Cimetidine, Probenecid) on Pharmacokinetics of a Transporter Probe Drug Cocktail Consisting of Digoxin, Furosemide, Metformin and Rosuvastatin (an Open-label, Randomised, Crossover Trial in Three Parts)PHASE1

COMPLETED · via probenecid · NCT03307252

A Phase 1, Open-Label, Non-Randomized, Fixed-Sequence Composite Study to Evaluate the Effects of Probenecid, Rifampin, and Verapamil on the Pharmacokinetics and Pharmacodynamics of Bexagliflozin in Healthy SubjectsPHASE1

COMPLETED · via probenecid · NCT03296800

Assessment of a New "Boosting" Strategy for HIV Pre-exposure Prophylaxis in Healthy VolunteersEARLY_PHASE1

COMPLETED · via probenecid · NCT03202511

A Phase 1, Randomized, Open-label, Crossover Study to Evaluate the Effect of the Organic Anion Transporter Inhibitor Probenecid on the Pharmacokinetics of JNJ-64041575 in Healthy Adult SubjectsPHASE1

COMPLETED · via probenecid · NCT03105986

An Open-label, Randomized, 2-treatment, 2-period, Crossover Study to Evaluate the Effect of Probenecid on the Pharmacokinetics of Pexidartinib in Healthy SubjectsPHASE1

COMPLETED · via probenecid · NCT03138759

ANK-dependent ATP Efflux Causes Calcium Pyrophosphate Deposition in CartilageEARLY_PHASE1

COMPLETED · via probenecid · NCT02243631

ClinicalTrials.gov via the drug-target graph.

What's happening now

1

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Trial status changed2026-09-03

    An Open-label, Phase 1 Study to Individually Characterize the Food Effect, the Drug-Drug Interaction Effect of OAT Inhibition, and the Drug-Drug Interaction Effect of P-glycoprotein Inhibition on the Pharmacokinetics of MK-8527 in Healthy Adult Participants

    Status changed to Active, not recruiting · ClinicalTrials.gov · via probenecid

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.