Glyburide

Summary

Glyburide (CHEMBL472) is an approved small-molecule hypoglycemic agent (ATC A10BB01) targeting SLCO2B1, KCNJ8, and KCNJ11; indicated across 9 conditions including diabetes mellitus and type 2 diabetes mellitus.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: A10BB01
• Targets: 4 (SLCO2B1, KCNJ8, KCNJ11…)
• Indications: 9 conditions
• Clinical trials: 81
• Chemistry: 494 Da · C23H28ClN3O5S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL472
Name	Glyburide
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	3488
ChEBI	CHEBI:5441
ATC	A10BB01
Molecular formula	C23H28ClN3O5S
Molecular weight	494
InChIKey	ZNNLBTZKUZBEKO-UHFFFAOYSA-N

SMILES: COC1=C(C=C(C=C1)Cl)C(=O)NCCC2=CC=C(C=C2)S(=O)(=O)NC(=O)NC3CCCCC3

IUPAC name: 5-chloro-N-[2-[4-(cyclohexylcarbamoylsulfamoyl)phenyl]ethyl]-2-methoxybenzamide

ChEBI definition: An N-sulfonylurea that is acetohexamide in which the acetyl group is replaced by a 2-(5-chloro-2-methoxybenzamido)ethyl group.

Pharmacological roles (ChEBI): hypoglycemic agent, anti-arrhythmia drug, EC 2.7.1.33 (pantothenate kinase) inhibitor, EC 3.6.3.49 (channel-conductance-controlling ATPase) inhibitor.

Also known as: Amglidia, Calabren, Cirara, Daonil, Diabeta, Diabetamide 2.5, Diabetamide 5, Euglucon, Glibenclamida, Glibenclamide, Glibenclamidum, Gliken

Patent coverage: 15,014 distinct patent families (53,236 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 52,496 (99%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
SLCO2B1	OATP2B1	Inhibition		0%	O94956
KCNJ8	Kir6.1			0%	Q15842
KCNJ11	Kir6.2			0.1%	Q14654
CFTR	CFTR	Pore blocker	4.66	0.1%	P13569

Broader ChEMBL bioactivity targets: 37 (assay-derived). Sample: Microtubule-associated protein tau, Nuclear receptor ROR-gamma, Fructose-bisphosphate aldolase, Prelamin-A/C, RecQ-like DNA helicase BLM, Inositol monophosphatase 1, Peripheral myelin protein 22, Solute carrier organic anion transporter family member 1B1, NACHT, LRR and PYD domains-containing protein 3, ATP-binding cassette sub-family C member 4.

Bioactivity

ChEMBL activities: 46 potent at pChembl ≥ 5 of 75 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ABCC8	8.37	IC50	4.3	nM	CHEMBL_ACT_337286
TSHR	6.9	Potency	125.9	nM	CHEMBL_ACT_3915506
ABCC9	6.89	Ki	130	nM	CHEMBL_ACT_483197
ABCC9	6.66	IC50	220	nM	CHEMBL_ACT_337284
PPARG	6.18	Ki	660	nM	CHEMBL_ACT_18960167
SLCO1B1	5.85	IC50	1400	nM	CHEMBL_ACT_15448315
ABCB11	5.82	IC50	1500	nM	CHEMBL_ACT_18051959
O35956	5.8	Ki	1600	nM	CHEMBL_ACT_11002333
CYP2C9	5.79	IC50	1602	nM	CHEMBL_ACT_7676850
CISD1	5.78	Ki	1671	nM	CHEMBL_ACT_16766171
HIF1A	5.7	Potency	1995	nM	CHEMBL_ACT_4126801
HIF1A	5.7	Potency	1995	nM	CHEMBL_ACT_4520212
CYP2C9	5.7	Potency	1995	nM	CHEMBL_ACT_5025363
CYP2C9	5.7	AC50	1995	nM	CHEMBL_ACT_5999062
SLCO1B1	5.66	IC50	2200	nM	CHEMBL_ACT_15448323
PPARG	5.64	EC50	2300	nM	CHEMBL_ACT_24989785
CYP2C9	5.6	Potency	2512	nM	CHEMBL_ACT_5029436
O70127	5.55	IC50	2800	nM	CHEMBL_ACT_15460363
HIF1A	5.5	Potency	3162	nM	CHEMBL_ACT_4131601
HIF1A	5.5	Potency	3162	nM	CHEMBL_ACT_4519124
CYP3A4	5.4	Potency	3981	nM	CHEMBL_ACT_4977665
CYP3A4	5.4	Potency	3981	nM	CHEMBL_ACT_4997843
CYP3A4	5.4	Potency	3981	nM	CHEMBL_ACT_5042898
CYP3A4	5.4	Potency	3981	nM	CHEMBL_ACT_5066552
CYP3A4	5.4	AC50	3981	nM	CHEMBL_ACT_6032054
ABCB11	5.3	IC50	5000	nM	CHEMBL_ACT_18129027
ABCB11	5.28	IC50	5300	nM	CHEMBL_ACT_15460431
ABCB11	5.28	IC50	5300	nM	CHEMBL_ACT_22396455
ABCB11	5.22	AC50	6000	nM	CHEMBL_ACT_25127164
O70127	5.21	Ki	6100	nM	CHEMBL_ACT_11003212

Target pathways

Aggregated over 4 target gene(s): SLCO2B1, KCNJ8, KCNJ11, CFTR.

Top Reactome pathways

33 total, by targets touching each:

Pathway	Targets	Genes
Neuronal System	2	KCNJ11, KCNJ8
ATP sensitive Potassium channels	2	KCNJ11, KCNJ8
Inwardly rectifying K+ channels	2	KCNJ11, KCNJ8
Potassium Channels	2	KCNJ11, KCNJ8
Transport of small molecules	2	KCNJ11, SLCO2B1
ABC-family protein mediated transport	2	CFTR, KCNJ11
Metabolism	1	KCNJ11
Integration of energy metabolism	1	KCNJ11
Disease	1	KCNJ11
Heme degradation	1	SLCO2B1
Muscle contraction	1	KCNJ11
Regulation of insulin secretion	1	KCNJ11
Transport of vitamins, nucleosides, and related molecules	1	SLCO2B1
SLC-mediated transmembrane transport	1	SLCO2B1
Cardiac conduction	1	KCNJ11
Ion homeostasis	1	KCNJ11
ABC transporter disorders	1	KCNJ11
Disorders of transmembrane transporters	1	KCNJ11
RHO GTPases regulate CFTR trafficking	1	CFTR
Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome	1	KCNJ11
Defective CFTR causes cystic fibrosis	1	CFTR
Defective ABCC8 can cause hypo- and hyper-glycemias	1	KCNJ11
Ub-specific processing proteases	1	CFTR
Organic anion transport by SLCO transporters	1	SLCO2B1
Cargo recognition for clathrin-mediated endocytosis	1	CFTR
Clathrin-mediated endocytosis	1	CFTR
RHOQ GTPase cycle	1	CFTR
Chaperone Mediated Autophagy	1	CFTR
Late endosomal microautophagy	1	CFTR
Aggrephagy	1	CFTR

Dominant GO biological processes

GO term	Targets
monoatomic ion transport	4
monoatomic ion transmembrane transport	3
transmembrane transport	2
transport across blood-brain barrier	2
response to hypoxia	2
response to ischemia	2
ventricular cardiac muscle tissue development	2
potassium ion transport	2
apoptotic process	2
determination of adult lifespan	2
response to xenobiotic stimulus	2
response to ATP	2
regulation of monoatomic ion transmembrane transport	2
response to endoplasmic reticulum stress	2
CAMKK-AMPK signaling cascade	2

Indications & clinical

Indications

9 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
diabetes mellitus	4	MONDO:0005015	EFO:0000400
type 2 diabetes mellitus	4	MONDO:0005148	MONDO:0005148
gestational diabetes	3	MONDO:0005406	EFO:0004593
stroke disorder	2	MONDO:0005098	EFO:0000712
brain injury	2	MONDO:0043510	MONDO:0043510
type 1 diabetes mellitus	2	MONDO:0005147	MONDO:0005147
spinal cord injury	1	MONDO:0043797	EFO:1001919

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 81.

Phase distribution

Phase	Trials
PHASE4	21
PHASE3	17
PHASE1	14
Not specified	13
PHASE2	7
PHASE1/PHASE2	6
PHASE2/PHASE3	2
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00123643	PHASE4	COMPLETED	Vascular Effects of Rosiglitazone Versus Glyburide in Type 2 Diabetic Patients
NCT00160485	PHASE4	WITHDRAWN	Glyburide Compared to Insulin in the Management of White’s Classification A2 Gestational Diabetes
NCT00347100	PHASE4	COMPLETED	Insulin Glargine in Type 2 Diabetic Patients
NCT00472875	PHASE4	UNKNOWN	Do Sulphonylureas Preserve Cortical Function During Hypoglycaemia?
NCT00494312	PHASE4	COMPLETED	Safety Study of Pioglitazone Compared To Glyburide on Liver Function
NCT00744965	PHASE4	COMPLETED	Treatment of Mild Gestational Diabetes With Glyburide Versus Placebo
NCT00770835	PHASE4	COMPLETED	Efficacy and Safety of Pioglitazone in Treating Subjects With Vascular Complications Associated With Type 2 Diabetes Mellitus.
NCT01456650	PHASE4	COMPLETED	R230C and C230C Variants of ABCA1 and Glyburide Response
NCT01563120	PHASE4	COMPLETED	A Comparison Between Two Oral Hypoglycemics - Metformin and Glybenclamide for the Treatment of Gestational Diabetes Mellitus
NCT01605773	PHASE4	COMPLETED	Effect of Repaglinide on Postprandial Lipemia in Type 2 Diabetes
NCT01698931	PHASE4	COMPLETED	Efficacy of Repaglinide in Subjects With Type 2 Diabetes
NCT01947699	PHASE4	WITHDRAWN	Glycemic Profile in Women With Gestational Diabetes Treated With Glyburide
NCT02091336	PHASE4	UNKNOWN	Oral Antidiabetic Agents in Pregnancy
NCT02145611	PHASE4	COMPLETED	Vildagliptin vs. Glibenclamide in Endothelial Function in Type 2 Diabetes and Hypertension
NCT02201602	PHASE4	COMPLETED	Sulphonylurea Receptor Mutation and Responsiveness to Gliclazide - a Pilot Proof of Concept, Randomised Cross-over Study
NCT02318693	PHASE4	COMPLETED	Efficacy of Sitagliptin and Glibenclamide on the Glucose Variability in Japanese Participants With Type 2 Diabetes Mellitus (MK-0431-355)
NCT02919345	PHASE4	COMPLETED	Assessment of Dapagliflozin Effect on Diabetic Endothelial Dysfunction of Brachial Artery
NCT03029702	PHASE4	COMPLETED	Metabolic Analysis for Treatment Choice in Gestational Diabetes Mellitus
NCT03078725	PHASE4	WITHDRAWN	Failure Rate of GLyburide And Metformin Among Gestational Diabetics
NCT03569540	PHASE4	UNKNOWN	Glibenclamide in Aneurysmatic Subarachnoid Hemorrhage
NCT05137678	PHASE4	UNKNOWN	Evaluate the Use of Glibenclamide on Acute aSAH
NCT00035542	PHASE3	COMPLETED	A Research Study to Determine the Safety and Efficacy of Glucovance Compared to Metformin and Glyburide in Children and Adolescents With Type 2 Diabetes.
NCT00046462	PHASE3	COMPLETED	Determine Whether Glycemic Control is Different Between Lantus & a 3rd Oral Agent When Failure With Other Treatment
NCT00251940	PHASE3	TERMINATED	GALLANT 7 Tesaglitazar Add-on to Sulphonylurea
NCT00255541	PHASE3	TERMINATED	GALLANT 4 Tesaglitazar vs. Glibenclamide
NCT00267683	PHASE3	TERMINATED	Efficacy and Safety of Insulin Aspart Versus Glibenclamide in Type 2 Diabetes
NCT00279045	PHASE3	COMPLETED	Diabetes Study With Rosiglitazone Monotherapy Versus Metformin Or Glyburide/Glibenclamide
NCT00286468	PHASE3	COMPLETED	Study of Alogliptin Combined With Sulfonylurea in Subjects With Type 2 Diabetes Mellitus.
NCT00313313	PHASE3	COMPLETED	A Study of Saxagliptin in Subjects With Type 2 Diabetes Who Have Inadequate Blood Sugar Control With Sulfonylureas
NCT00393718	PHASE3	COMPLETED	Effect of Liraglutide on Blood Glucose Control in Subjects With Type 2 Diabetes
NCT00515801	PHASE2/PHASE3	COMPLETED	Sulfonylurea Effects on Glucagon Regulation During Hypoglycemia in Type 1 DM
NCT00521742	PHASE3	COMPLETED	Efficacy of Pioglitazone Compared to Glyburide in Treating Subjects With Type 2 Diabetes Mellitus and Mild Cardiac Disease
NCT00521820	PHASE3	TERMINATED	Safety Comparison of Pioglitazone and Glyburide in Type 2 Diabetes Subjects With Mild to Moderate Congestive Heart Failure
NCT00759720	PHASE3	TERMINATED	Efficacy and Safety of TAK-559 Combined With Glyburide in Treating Subjects With Type 2 Diabetes Mellitus.
NCT01731431	PHASE3	COMPLETED	Multicenter Randomized Trial of Non-inferiority Between Glyburide and Insulin for the Treatment of Gestational Diabetes
NCT01822548	PHASE3	COMPLETED	Effect of Vildagliptin vs. Glibenclamide on Circulating Endothelial Progenitor Cell Number Type 2 Diabetes
NCT02080377	PHASE3	COMPLETED	A Feasibility Study Looking at the Use of Glibenclamide and metfoRmin Versus stAndard Care in gEstational diabeteS
NCT02375828	PHASE3	COMPLETED	Glibentek in Patients With Neonatal Diabetes Secondary to Mutations in K+-ATP Channels
NCT03284463	PHASE2/PHASE3	COMPLETED	Safety and Efficacy of Glibenclamide Combined With Rt-PA in Acute Cerebral Embolism
NCT05688332	PHASE3	UNKNOWN	Glycaemic & Cardiovascular Treatment Outcomes of Voglibose Vs Glibenclamide Added to Metformin in T2DM Patients

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (2) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of DPWG Guideline for glyburide and CYP2C9	DPWG	CYP2C9
Annotation of CPIC Guideline for aminosalicylic acid, chloramphenicol,	CPIC	G6PD

PharmGKB also curates 4 clinical and 50 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

185 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
QUERCETIN	ChEMBL + PubChem	Phase 3 (approved)	CFTR, SLCO2B1
Rutin	ChEMBL + PubChem	Phase 3 (approved)	CFTR, SLCO2B1
GENISTEIN	ChEMBL + PubChem	Phase 2 (approved)	CFTR, SLCO2B1
CROMAKALIM	ChEMBL	Phase 2	KCNJ11, KCNJ8
ATAZANAVIR	ChEMBL + PubChem	Phase 4 (approved)	SLCO2B1
CYCLOSPORINE	ChEMBL + PubChem	Phase 4 (approved)	SLCO2B1
DIAZOXIDE	ChEMBL + PubChem	Phase 4 (approved)	KCNJ11
ERLOTINIB	ChEMBL + PubChem	Phase 4 (approved)	SLCO2B1
IVACAFTOR	ChEMBL + PubChem	Phase 4 (approved)	CFTR
PROPAFENONE	ChEMBL + PubChem	Phase 4 (approved)	KCNJ11
RIFAMPIN	ChEMBL + PubChem	Phase 4 (approved)	SLCO2B1
RIFAMYCIN	ChEMBL + PubChem	Phase 4 (approved)	SLCO2B1
RITONAVIR	ChEMBL + PubChem	Phase 4 (approved)	SLCO2B1
ELEXACAFTOR	ChEMBL	Phase 4 (approved)	CFTR
ELTROMBOPAG	ChEMBL	Phase 4 (approved)	SLCO2B1
LUMACAFTOR	ChEMBL	Phase 4 (approved)	CFTR
PINACIDIL	ChEMBL	Phase 4 (approved)	KCNJ11
SULFASALAZINE	ChEMBL	Phase 4 (approved)	SLCO2B1
TEZACAFTOR	ChEMBL	Phase 4 (approved)	CFTR
BAMOCAFTOR	ChEMBL	Phase 3	CFTR
EPIGALOCATECHIN GALLATE	ChEMBL	Phase 3	SLCO2B1
SILYBIN A	ChEMBL	Phase 3	SLCO2B1
CLAMIKALANT	ChEMBL	Phase 2	KCNJ11
FISETIN	ChEMBL	Phase 2	SLCO2B1
GALICAFTOR	ChEMBL	Phase 2	CFTR
GLPG-2737	ChEMBL	Phase 2	CFTR
ICENTICAFTOR	ChEMBL	Phase 2	CFTR
ISOQUERCETIN	ChEMBL	Phase 2	SLCO2B1
LUTEOLIN	ChEMBL	Phase 2	SLCO2B1
NAVOCAFTOR	ChEMBL	Phase 2	CFTR
RISELCAFTOR	ChEMBL	Phase 2	CFTR
SILICRISTIN	ChEMBL	Phase 2	SLCO2B1
TIFENAZOXIDE	ChEMBL	Phase 2	KCNJ11
Acetic Acid	PubChem	Approved	SLCO2B1
Acyclovir	PubChem	Approved	SLCO2B1
Allopurinol	PubChem	Approved	SLCO2B1
Amantadine	PubChem	Approved	SLCO2B1
aminohippuric acid	PubChem	Approved	SLCO2B1
Amitriptyline	PubChem	Approved	SLCO2B1
Amprenavir	PubChem	Approved	SLCO2B1
anhydrous citric acid	PubChem	Approved	SLCO2B1
Atenolol	PubChem	Approved	SLCO2B1
Atomoxetine	PubChem	Approved	SLCO2B1
Atorvastatin	PubChem	Approved	SLCO2B1
Benzoic Acid	PubChem	Approved	SLCO2B1
Berberine Chloride	PubChem	Approved	KCNJ11
Budesonide	PubChem	Approved	SLCO2B1
Bupropion	PubChem	Approved	SLCO2B1
Buspirone	PubChem	Approved	SLCO2B1
Caffeine	PubChem	Approved	SLCO2B1
Candesartan	PubChem	Approved	SLCO2B1
Captopril	PubChem	Approved	SLCO2B1
Carbamazepine	PubChem	Approved	SLCO2B1
Cefadroxil	PubChem	Approved	SLCO2B1
Celecoxib	PubChem	Approved	SLCO2B1
Cetirizine	PubChem	Approved	SLCO2B1
Chloroquine	PubChem	Approved	SLCO2B1
Chlorpromazine	PubChem	Approved	SLCO2B1
Chlorzoxazone	PubChem	Approved	SLCO2B1
Cholic Acid	PubChem	Approved	SLCO2B1