Repaglinide

Summary

Repaglinide (CHEMBL1272) is an approved small molecule (ATC A10BX02) targeting ABCC8; indicated across 15 conditions including diabetes mellitus and type 2 diabetes mellitus.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: A10BX02
• Targets: 1 (ABCC8)
• Indications: 15 conditions
• Clinical trials: 65
• Chemistry: 452.6 Da · C27H36N2O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1272
Name	Repaglinide
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	65981
ATC	A10BX02
Molecular formula	C27H36N2O4
Molecular weight	452.6
InChIKey	FAEKWTJYAYMJKF-QHCPKHFHSA-N

SMILES: CCOC1=C(C=CC(=C1)CC(=O)N[C@@H](CC(C)C)C2=CC=CC=C2N3CCCCC3)C(=O)O

IUPAC name: 2-ethoxy-4-[2-[[(1S)-3-methyl-1-(2-piperidin-1-ylphenyl)butyl]amino]-2-oxoethyl]benzoic acid

Also known as: A10BX02, AG-EE 623 ZW, AG-EE-623ZW, AGEE-623ZW, Enyglid, Novonorm, NSC-759893, Prandin, Repaglinida, Repaglinide, Repaglinide accord, Repaglinide component of prandimet

Patent coverage: 8,142 distinct patent families (33,453 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 33,299 (100%) 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
ABCC8	ATP-binding cassette, sub-family C (CFTR/MRP), member 8	Inhibition	6.97	0%	Q09428

Broader ChEMBL bioactivity targets: 19 (assay-derived). Sample: Nuclear receptor ROR-gamma, Fructose-bisphosphate aldolase, Prelamin-A/C, ATP-binding cassette sub-family C member 4, Bile acid receptor, ATP-binding cassette sub-family C member 8, 5-hydroxytryptamine receptor 2A, Alpha-1A adrenergic receptor, Prostaglandin G/H synthase 2, Adenosine receptor A3.

Bioactivity

ChEMBL activities: 10 potent at pChembl ≥ 5 of 24 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ABCC8	7.3	Kd	50	nM	CHEMBL_ACT_1454077
ABCC8	6.97	IC50	106	nM	CHEMBL_ACT_1454078
LMNA	6.4	Potency	398.1	nM	CHEMBL_ACT_3661659
NR1I3	5.3	AC50	5000	nM	CHEMBL_ACT_25164314
MAPK1	5.2	Potency	6310	nM	CHEMBL_ACT_4725521
NR1H4	5.19	AC50	6500	nM	CHEMBL_ACT_25234593
SLC22A1	5.04	IC50	9200	nM	CHEMBL_ACT_2364167
ABCB11	5.03	AC50	9327	nM	CHEMBL_ACT_25126966
HTR2A	5.03	AC50	9400	nM	CHEMBL_ACT_25225085
PDE4D	5.02	AC50	9600	nM	CHEMBL_ACT_25185231

Target pathways

Aggregated over 1 target gene(s): ABCC8.

Top Reactome pathways

11 total, by targets touching each:

Pathway	Targets	Genes
Neuronal System	1	ABCC8
ATP sensitive Potassium channels	1	ABCC8
Inwardly rectifying K+ channels	1	ABCC8
Potassium Channels	1	ABCC8
Metabolism	1	ABCC8
Integration of energy metabolism	1	ABCC8
Disease	1	ABCC8
Regulation of insulin secretion	1	ABCC8
ABC transporter disorders	1	ABCC8
Disorders of transmembrane transporters	1	ABCC8
Defective ABCC8 can cause hypo- and hyper-glycemias	1	ABCC8

Dominant GO biological processes

GO term	Targets
action potential	1
intracellular glucose homeostasis	1
potassium ion transport	1
female pregnancy	1
memory	1
visual learning	1
response to pH	1
response to xenobiotic stimulus	1
response to zinc ion	1
negative regulation of low-density lipoprotein particle clearance	1
negative regulation of angiogenesis	1
cellular response to nutrient levels	1
response to lipopolysaccharide	1
positive regulation of tumor necrosis factor production	1
response to insulin	1

Indications & clinical

Indications

15 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
hypertensive disorder	3	MONDO:0005044	EFO:0000537
atherosclerosis	3	MONDO:0005311	EFO:0003914
coronary artery disorder	3	MONDO:0005010	EFO:0001645
cystic fibrosis	3	MONDO:0009061	MONDO:0009061
rheumatoid arthritis	1	MONDO:0008383	EFO:0000685
malaria	1	MONDO:0005136	EFO:0001068
Parkinson disease	1	MONDO:0005180	MONDO:0005180
gastrointestinal stromal tumor	1	MONDO:0011719	MONDO:0011719
inborn mitochondrial metabolism disorder	1	MONDO:0004069	MONDO:0044970
neoplasm	1	MONDO:0005070	EFO:0000616
sickle cell disease	1	MONDO:0011382	MONDO:0011382

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

Clinical trials

Total trials: 65.

Phase distribution

Phase	Trials
PHASE1	31
PHASE4	19
Not specified	10
PHASE3	4
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00118950	PHASE4	COMPLETED	Effect of Metformin Versus Repaglinide Treatment in Non-Obese Type 2 Diabetic Patients Uncontrolled by Diet
NCT00118963	PHASE4	COMPLETED	Effect of Repaglinide Versus Metformin Treatment in Non-Obese Patients With Type-2-Diabetes
NCT00336310	PHASE4	UNKNOWN	A Double-Blind, Randomized, Parallel, Comparative Study to Evaluate the Efficacy and Safety of an Antidiabetic Agent Repaglinide for the Treatment of Type 2 Diabetes Mellitus Patients
NCT00491725	PHASE4	COMPLETED	Efficacy and Safety of Repaglinide and Metformin Combination Therapy in Type 2 Diabetes Failing on Oral Anti-diabetic Drugs
NCT00568074	PHASE4	COMPLETED	Efficacy and Safety of Repaglinide, Glurenorm® and Glucobay® in Chinese Subjects With Type 2 Diabetes
NCT00568984	PHASE4	COMPLETED	Efficacy and Safety of Repaglinide and Metformin Combined in Type 2 Diabetes
NCT00799448	PHASE4	TERMINATED	Comparison of Efficacy and Safety of Repaglinide Combined With Insulin NPH Versus Biphasic Human Insulin 30 Alone in Inadequately Controlled Subjects With Type 2 Diabetes
NCT00819741	PHASE4	COMPLETED	Comparison of the Blood Sugar Lowering Effect Between Repaglinide Plus Metformin and Repaglinide Alone in Type 2 Diabetics Not Previously Treated With Oral Sugar-lowering Drugs
NCT01022762	PHASE4	COMPLETED	Comparison of Repaglinide and Gliclazide in Chinese Subjects With Type 2 Diabetes Never Received Oral Antidiabetic Drug Treatment
NCT01465152	PHASE4	COMPLETED	Comparison of Metformin, Repaglinide or the Combination of Both in Subjects With Type 2 Diabetes
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
NCT01709305	PHASE4	COMPLETED	A Study of the Safety and Efficacy of Glimepiride, Gliclazide, Repaglinide or Acarbose When Added to Sitagliptin + Metformin Combination Therapy in Chinese Participants With Diabetes (MK-0431-313)
NCT01720290	PHASE4	COMPLETED	Comparison of Repaglinide and Metformin Administered Alone or in Combination in Type 2 Diabetes
NCT01720303	PHASE4	COMPLETED	Efficacy and Safety of Repaglinide Combined With Insulin in Type 2 Diabetes
NCT02040246	PHASE4	COMPLETED	Comparison of Metformin and Repaglinide Monotherapy in the Treatment of New Onset Type 2 Diabetes Mellitus in China
NCT02694263	PHASE4	COMPLETED	Canagliflozin (Invokana™) vs. Standard Dual Therapy Regimen for T2DM During Ramadan
NCT03359837	PHASE4	COMPLETED	Comparison of Two Treatment Regimens in Patients With Type 2 Diabetes After Short-term Intensive Insulin Therapy
NCT03824002	PHASE4	COMPLETED	Dulaglutide in Diabetic Patients, Relationship Between Arterial Stiffness, Endothelial Function, Clinical and Laboratory Variables
NCT00072904	PHASE3	COMPLETED	Diabetes Therapy to Improve BMI and Lung Function in CF
NCT00399711	PHASE3	COMPLETED	Effect of Repaglinide and Metformin Combination Tablet or Rosiglitazone and Metformin in Fixed Dose Combination on Blood Glucose Control in Patients With Type 2 Diabetes
NCT00662714	PHASE3	COMPLETED	Early Diagnosis of Diabetes Mellitus in Patients With Cystic Fibrosis
NCT01562561	PHASE3	COMPLETED	Efficacy and Safety of Repaglinide Combined With Insulin NPH in Subjects With Type 2 Diabetes
NCT05384626	PHASE1/PHASE2	RECRUITING	A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
NCT06601517	PHASE1	NOT_YET_RECRUITING	A Drug-Drug Interaction (DDI) Study of HDM1002 With Repaglinide, Atorvastatin, Digoxin and Rosuvastatin in Healthy Subjects and Overweight Subjects.
NCT07340190	PHASE1	NOT_YET_RECRUITING	A Drug-drug Interaction Study to Evaluate the Effects of Pelabresib on the Pharmacokinetics of Repaglinide, Midazolam, and Combined Oral Contraceptive in Patients With Advanced Malignancies
NCT00959101	PHASE1	COMPLETED	Comparison of Repaglinide and Metformin Combination Tablet Versus Repaglinide and Metformin as Separate Tablets in Healthy Volunteers
NCT01489644	PHASE1	COMPLETED	Single Dose Pharmacokinetics of Repaglinide, Metformin and Combination Tablet in Healthy Volunteers
NCT01490658	PHASE1	COMPLETED	Single Dose Pharmacokinetics of Repaglinide, Metformin and Combination Tablet in Fed Healthy Volunteers
NCT01536366	PHASE1	COMPLETED	Effect of BIA 9-1067 on the Pharmacokinetics of Repaglinide
NCT01780051	PHASE1	COMPLETED	A Pharmacokinetic Study to Compare Co-administration of Repaglinide and Metformin HCl to Administration of Combination Preparation of Those Two Components
NCT01797198	PHASE1	COMPLETED	A Study to Assess the Effect of Multiple Doses of Gemfribozil on a Single Dose of ASP3652, and to Assess the Effects of Multiple Doses of ASP3652 on a Single Dose of Repaglinide in the Body of Healthy Subjects
NCT02128321	PHASE1	COMPLETED	A Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of Repaglinide and Caffeine
NCT02305901	PHASE1	COMPLETED	The Effect of Multiple Doses of BI 187004 on the Single-dose Pharmacokinetics of Repaglinide and Bupropion in Healthy Male Volunteers
NCT03028103	PHASE1	COMPLETED	Open-Label, Multicenter, Two-Part, Phase 1 Study to Characterize Effects of a Moderate CYP3A Inhibitor on PK of Tazemetostat, Effects of Tazemetostat on PK of CYP2C8 and CYP2C19 Substrates, and Effect of Increased Gastric pH on PK of Tazemetostat in B-cell Lymphoma or Advanced Solid Tumor Patients
NCT03723395	PHASE1	COMPLETED	A Drug-Drug Interaction Study in Healthy Volunteers of the Effects of Tucatinib
NCT04008186	PHASE1	COMPLETED	A Clinical Drug-Drug Interaction (DDI) Study With Omaveloxolone
NCT04457180	PHASE1	COMPLETED	A Pharmacokinetic Interaction Study Between Apatinib Mesylate and Repaglinide or Bupropion in Advanced Solid Tumor Subjects
NCT04530981	PHASE1	COMPLETED	A Drug-Drug Interaction Study to Evaluate the Effect of Ripretinib on the Pharmacokinetics of a CYP2C8 Probe Substrate in Patients with Advanced GIST
NCT04643249	PHASE1	COMPLETED	Drug-drug Interaction Study of KL1333 in Healthy Subjects

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 17 clinical and 29 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.

6 molecules share ≥1 primary target. Top 6 by shared-target count:

Molecule	Source	Status	Shared targets
DIAZOXIDE	ChEMBL + PubChem	Phase 4 (approved)	ABCC8
GLYBURIDE	ChEMBL + PubChem	Phase 4 (approved)	ABCC8
CLAMIKALANT	ChEMBL	Phase 2	ABCC8
CROMAKALIM	ChEMBL	Phase 2	ABCC8
TIFENAZOXIDE	ChEMBL	Phase 2	ABCC8
Berberine Chloride	PubChem	Approved	ABCC8