Protein / target

ATP-sensitive inward rectifier potassium channel 11

KCNJ11Q14654Homo sapiensSwiss-Prot
UniProt: Q14654Ensembl: ENSG00000187486HGNC: HGNC:6257NCBI Gene: 3767
Clinically validated
Therapeutic maturity
15
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

ATP-activated inward rectifier potassium channel activity

Primary system

Endocrine & metabolic

Strongest disease association

diabetes mellitus, permanent neonatal 2

Genetic evidence · score 0.96

Therapeutic maturity

Clinically validated target

15 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

15 approved

30 linked trials

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

Inward rectifier potassium channel that forms the pore of ATP-sensitive potassium channels (KATP), regulating potassium permeability as a function of cytoplasmic ATP and ADP concentrations in many different cells (PubMed:29286281, PubMed:34815345). Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium (By similarity). In pancreatic cells, it forms KATP channels with ABCC8/SUR1 (PubMed:29286281, PubMed:34815345). Can form cardiac and smooth muscle-type KATP channels with ABCC9

Subcellular location

Membrane
Domains and Gene Ontology detail (22)

Gene Ontology

  • Ccytoplasm
  • Cinward rectifying potassium channel
  • Cplasma membrane
  • CT-tubule
  • Fankyrin binding
  • FATP binding
  • FATP-activated inward rectifier potassium channel activity
  • FATPase-coupled monoatomic cation transmembrane transporter activity
  • Fpotassium ion binding
  • Ftransmembrane transporter binding
  • Fvoltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential
  • Fvoltage-gated potassium channel activity

390 aa · 44 kDa · 2 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Ion channel gatingGOSynaptic signallingGOImmune signallingUniProtMetabolic enzyme activityGO
View supporting evidence

Ion channel gating

  • ·ATPase-coupled monoatomic cation transmembrane transporter activity
  • ·voltage-gated monoatomic ion channel activity involved in regulation of presynaptic memb…
  • ·potassium ion transmembrane transport

Synaptic signalling

  • ·voltage-gated monoatomic ion channel activity involved in regulation of presynaptic memb…

Immune signalling

  • ·Inward rectifier potassium channel that forms the pore of ATP-sensitive potassium channe…

Metabolic enzyme activity

  • ·glucose metabolic process
View underlying pathways (6)
ATP sensitive Potassium channels
ABC-family protein mediated transport
Regulation of insulin secretion
Ion homeostasis
Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome
Defective ABCC8 can cause hypo- and hyper-glycemias

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

ABCC8ABCC9KCNJ8DIABLO…DIABLOGABBR1GABBR2GCKXIAPINSKCNJ11

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Drugs targeting this protein

2

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

Glyburide
ApprovedBlocker

Sulfonylurea receptor 1, Kir6.2 blocker

Appears in clinical studies involving type 2 diabetes mellitus, diabetes mellitus, Stroke, coronary artery disorder

Acts on a complex — shared with ABCC8 · 1 of 2 recorded protein targets — narrow recorded profile

glimepiride
ApprovedBlocker

Sulfonylurea receptor 1, Kir6.2 blocker

Appears in clinical studies involving type 2 diabetes mellitus, diabetes mellitus, type 2 diabetes mellitus, coronary artery disorder

Acts on a complex — shared with ABCC8 · 1 of 2 recorded protein targets — narrow recorded profile

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

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

diabetes mellitus, permanent neonatal 20.96

Genetic · overall 0.81

hyperinsulinemic hypoglycemia, familial, 20.96

Genetic · overall 0.84

type 2 diabetes mellitus0.93

Genetic · overall 0.86

permanent neonatal diabetes mellitus0.92

Genetic literature · overall 0.73

diabetes mellitus0.90

Genetic · overall 0.79

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

MODY0.30

Clinical · overall 0.70

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

diabetes mellitus, transient neonatal, 30.80

Genetic

transient neonatal diabetes mellitus0.72

Genetic literature

autosomal dominant hyperinsulinism due to Kir6.2 deficiency0.69

Genetic literature

diazoxide-resistant focal hyperinsulinism due to Kir6.2 deficiency0.69

Genetic literature

Show all associations
type 2 diabetes mellitus0.86
hyperinsulinemic hypoglycemia, familial, 20.84
diabetes mellitus, permanent neonatal 20.81
diabetes mellitus, transient neonatal, 30.80
diabetes mellitus0.79
permanent neonatal diabetes mellitus0.73
transient neonatal diabetes mellitus0.72
MODY0.70
autosomal dominant hyperinsulinism due to Kir6.2 deficiency0.69
diazoxide-resistant focal hyperinsulinism due to Kir6.2 deficiency0.69

Open Targets ranks 1,789 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 15 total

GLIPIZIDEApproval

type 2 diabetes mellitus · diabetes mellitus · coronary artery disorder

CHLORPROPAMIDEApproval

diabetes mellitus · type 2 diabetes mellitus · type 2 diabetes mellitus

REPAGLINIDEApproval

type 2 diabetes mellitus · diabetes mellitus · type 2 diabetes mellitus

MITIGLINIDE CALCIUM DIHYDRATEApproval

type 2 diabetes mellitus · type 2 diabetes mellitus

GLIMEPIRIDEApproval

type 2 diabetes mellitus · diabetes mellitus · type 2 diabetes mellitus

ACETOHEXAMIDEApproval

diabetes mellitus

TOLAZAMIDEApproval

type 2 diabetes mellitus · diabetes mellitus

MINOXIDILApproval

hypotrichosis · hypertensive disorder · Hypertension

DIAZOXIDEApproval

hyperinsulinemic hypoglycemia · pancreatic insulinoma · hyperinsulinism

NATEGLINIDEApproval

type 2 diabetes mellitus · diabetes mellitus · type 2 diabetes mellitus

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · GO CC high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule BinderOC · Advanced Clinical

Safety liabilities

abnormal pulseincreased/decreased blood glucoseincreased urinary sodium excretiondecreased heart ratedecreased blood glucosecardiac lesionsdecreased blood pressureincreased heart ratecardiac arrhythmiaatrioventricular blockdecreased blood insulindecreased convulsions

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.

Influence of Improving Glycaemic Control on Glucagon-Like-Peptide-1 Response to an Oral Glucose Load. Comparison of Sulphonylurea With DPP-4 Inhibition.NA

COMPLETED · via glimepiride · NCT00747383

An Individualized treatMent aPproach for oldER patIents: A Randomized, Controlled stUdy in Type 2 Diabetes Mellitus (IMPERIUM)PHASE4

TERMINATED · via glimepiride · NCT02072096

A Phase III, Multicenter, Randomized, Open-label Clinical Trial Comparing the Efficacy and Safety of a Sitagliptin-Based Treatment Paradigm to a Liraglutide-Based Treatment Paradigm in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin MonotherapyPHASE3

COMPLETED · via glimepiride · NCT01296412

Liraglutide Effect and Action in Diabetes (LEAD-2): Effect on Glycaemic Control After Once Daily Administration of Liraglutide in Combination With Metformin Versus Metformin Monotherapy Versus Metformin and Glimepiride Combination Therapy in Subjects With Type 2 DiabetesPHASE3

COMPLETED · via glimepiride · NCT00318461

The Effect of Liraglutide on Endothelial Function in Subjects With Type 2 Diabetes Mellitus: A 12-week Randomized, Double-blind, Placebo-controlled, Parallel-group, Single-center Trial With an Open-label Glimepiride ArmPHASE3

COMPLETED · via glimepiride · NCT00620282

Effect of Liraglutide on Glycaemic Control in Subjects With Type 2 DiabetesPHASE3

COMPLETED · via Glyburide · NCT00393718

Show remaining trials (24)
Liraglutide Effect and Action in Diabetes (LEAD-3): Effect on Glycemic Control of Liraglutide Versus Glimepiride in Type 2 DiabetesPHASE3

TERMINATED · via glimepiride · NCT00294723

Effect of Liraglutide or Glimepiride Added to Metformin on Glycaemic Control in Subjects With Type 2 DiabetesPHASE3

COMPLETED · via glimepiride · NCT00614120

A Randomized, Controlled Trial Comparing the Effect of Exenatide, Sitagliptin or Glimepiride on Functional ß -Cell Mass in Patients With Impaired Fasting Glucose or Early Type 2 DiabetesNA

COMPLETED · via glimepiride · NCT00775684

Open-labelled, Randomized, Active-controlled, Parallel-arm, Single-center Study on Effect of Sitagliptin on T2DM Patients on Treatment With Metformin and InsulinPHASE4

COMPLETED · via glimepiride · NCT01341717

Transforming Hypertension Treatment in Nigeria Using a Type II Hybrid, Interrupted Time Series Design - Aim 3NA

NOT_YET_RECRUITING · via glimepiride · NCT07589387

A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial to Study the Safety and Efficacy of the Addition of MK-3102 to Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Combination Therapy With Glimepiride and MetforminPHASE3

COMPLETED · via glimepiride · NCT01704261

Double-blinded Comparative Study to Investigate the Efficacy and Safety of HOE490 O (Glimepiride and Metformin) Compared With Placebo on Top of Glimepiride in Patients With T2DM Inadequately Treated With Constant Dose of GlimepiridePHASE3

COMPLETED · via glimepiride · NCT00924573

Spinal Cord Injury Neuroprotection With Glyburide; Pilot Study: An Open-Label Prospective Evaluation of the Feasibility, Safety, Pharmacokinetics, and Preliminary Efficacy of Oral Glyburide (DiaBeta) in Patients With Acute Traumatic Spinal Cord InjuryPHASE1/PHASE2

TERMINATED · via Glyburide · NCT02524379

Single-Dose Fasting In Vivo Bioequivalence Study of Glimepiride Tablets (1 mg; Mylan) to Amaryl® Tablets (1 mg; Aventis) in Healthy VolunteersPHASE1

COMPLETED · via glimepiride · NCT00648362

The Effects of Saxagliptin 5mg, Once Daily for 52 Weeks on 24 Hour Urine Albumin Creatinine Rate(ACR) , in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycaemic Control on Metformin or/and AcarbosePHASE4

UNKNOWN · via glimepiride · NCT02462369

Evaluation of Safety and Efficacy of Glibenclamide in the Treatment of Severe Traumatic Brain InjuryPHASE1/PHASE2

UNKNOWN · via Glyburide · NCT05148403

A Single Randomized, Open, Cross-over, Phase Ie Study to Access the Drug-drug Interaction of SP2086 and GlyburidePHASE1

COMPLETED · via Glyburide · NCT02815787

Glibenclamide Advantage in Treating Edema After Intracerebral Hemorrhage (GATE-ICH): a Multi-center Randomized, Controlled, Assessor-blinded TrialNA

COMPLETED · via Glyburide · NCT03741530

Do Sulphonylureas Preserve Cortical Function During Hypoglycaemia?PHASE4

UNKNOWN · via Glyburide · NCT00472875

Efficacy of Repaglinide Compared to Glyburide and Placebo on Hepatic Glucose Metabolism in Type 2 Diabetic Subjects Treated With Diet or With Antidiabetic Oral Agents. A Randomized, Open, Cross-over Single-centre Placebo-controlled TrialPHASE4

COMPLETED · via Glyburide · NCT01698931

A Multicenter, Randomized, Double-Blind, Active-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of TAK-875 25 mg and 50 mg Compared to Glimepiride When Used in Combination With Metformin in Subjects With Type 2 DiabetesPHASE3

TERMINATED · via glimepiride · NCT01481116

The Hemodynamic Effects of PACAP38 After Glibenclamide Administration in Healthy VolunteersNA

COMPLETED · via Glyburide · NCT04960657

A Research Study to Determine the Safety and Efficacy of Glucovance Compared to Metformin and Glyburide in Children and Adolescents With Type 2 Diabetes.PHASE3

COMPLETED · via Glyburide · NCT00035542

A Multi-national, Open-labelled, Randomised, Parallel Group, 4 Week run-in and 26 Weeks Treat-to-target Comparison of Biphasic Insulin Aspart 30 Once Daily Versus Insulin Glargine Once Daily Both in Combination With Metformin and Glimepiride in Insulin naïve Subjects With Type 2 DiabetesPHASE4

COMPLETED · via glimepiride · NCT00469092

Sulphonylurea Receptor Mutation and Responsiveness to Gliclazide - a Pilot Proof of Concept, Randomised Cross-over StudyPHASE4

COMPLETED · via Glyburide · NCT02201602

Randomized, Three Period Cross Over, Double Blind, Double Dummy Study in Type 2 Diabetic Patients to Assess the Endothelial Effects of Linagliptin, Glimepiride and Placebo Therapy for 28 Days ('ENDOTHELINA')PHASE1

COMPLETED · via glimepiride · NCT01703286

The Effect of Glimepiride Compared With Sitagliptin as an add-on Therapy to Metformin in Severe Insulin Deficiency DiabetesPHASE4

UNKNOWN · via glimepiride · NCT05386186

Relative Bioavailability of Both BI 10773 and Glimepiride After Co-administration Compared to Multiple Oral Doses of BI 10773 (50 mg q.d.) Alone and a Single Dose of Glimepiride (1 mg) Alone in Healthy Male Volunteers (an Open-label, Randomised, Crossover, Clinical Phase I Study)PHASE1

COMPLETED · via glimepiride · NCT02172261

A Feasibility Study Looking at the Use of Glibenclamide and metfoRmin Versus stAndard Care in gEstational diabeteSPHASE3

COMPLETED · via Glyburide · NCT02080377

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

type 2 diabetes mellitusWell supported
0.99
agreement 0.90–1.00
Genetic41%Clinical33%Somatic mutation20%Literature6%Genetic literaturedup

Open Targets aggregate 0.86 · 4 independent evidence families · 1 not counted as duplicate

diabetes mellitusWell supported
0.98
agreement 0.88–1.00
Genetic48%Clinical39%Animal model8%Literature6%

Open Targets aggregate 0.79 · 4 independent evidence families

diabetes mellitus, permanent neonatal 2Well supported
0.96
agreement 0.84–1.00
Genetic89%Animal model12%Genetic literaturedup

Open Targets aggregate 0.81 · 2 independent evidence families · 1 not counted as duplicate

hyperinsulinemic hypoglycemia, familial, 2Well supported
0.96
agreement 0.84–1.00
Genetic89%Animal model11%Literature0%Genetic literaturedup

Open Targets aggregate 0.84 · 3 independent evidence families · 1 not counted as duplicate

diabetes mellitus, transient neonatal, 3Well supported
0.91
agreement 0.79–1.00
Genetic85%Animal model15%Literature0%Genetic literaturedup

Open Targets aggregate 0.80 · 3 independent evidence families · 1 not counted as duplicate

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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

8

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  1. Label change2026-06-30

    Label change: GLYBURIDE AND METFORMIN HYDROCHLORIDE (ANDA206748)

    fda · regulatory · fda · via Glyburide

  2. Label change2026-06-30

    Label change: GLYBURIDE AND METFORMIN HYDROCHLORIDE (ANDA206748)

    fda · regulatory · fda · via Glyburide

  3. New publication2019-10-25
    Pharmacological Inhibitors of the NLRP3 Inflammasome.

    Frontiers in immunology · 2019 · 518 citations · Europe PMC · via Glyburide

  4. Regulatory approval2018-05-24

    Approval: Amglidia (EMA)

    ema · regulatory · ema · via Glyburide

  5. Regulatory approval2016-02-29

    Approval: GLYBURIDE AND METFORMIN HYDROCHLORIDE (ANDA206748)

    fda · regulatory · fda · via Glyburide

  6. New publication2015-08-01
    Glyburide in Women With Mild Gestational Diabetes: A Randomized Controlled Trial.

    Obstetrics and gynecology · 2015 · 26 citations · Europe PMC · via Glyburide

  7. New publication2009-02-01
    Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy.

    Diabetes, obesity & metabolism · 2009 · 124 citations · Europe PMC · via Glyburide

  8. New publication2007-06-26
    Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin.

    Diabetes, obesity & metabolism · 2007 · 352 citations · Europe PMC · via glimepiride

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.