Chlorpropamide

Summary

Chlorpropamide (CHEMBL498) is an approved small-molecule hypoglycemic agent (ATC A10BB02) targeting ABCC8; indicated across 2 conditions including diabetes mellitus and type 2 diabetes mellitus.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: A10BB02
• Targets: 1 (ABCC8)
• Indications: 2 conditions
• Clinical trials: 1
• Chemistry: 276.74 Da · C10H13ClN2O3S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL498
Name	Chlorpropamide
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	2727
ChEBI	CHEBI:3650
ATC	A10BB02
Molecular formula	C10H13ClN2O3S
Molecular weight	276.74
InChIKey	RKWGIWYCVPQPMF-UHFFFAOYSA-N

SMILES: CCCNC(=O)NS(=O)(=O)C1=CC=C(C=C1)Cl

IUPAC name: 1-(4-chlorophenyl)sulfonyl-3-propylurea

ChEBI definition: An N-sulfonylurea that is urea in which a hydrogen attached to one of the nitrogens is substituted by 4-chlorobenzenesulfonyl group and a hydrogen attached to the other nitrogen is substituted by propyl group. Chlorpropamide is a hypoglycaemic agent used in the treatment of type 2 (non-insulin-dependent) diabetes mellitus not responding to dietary modification.

Pharmacological roles (ChEBI): hypoglycemic agent, insulin secretagogue.

Also known as: Chlorpropamide, Clorpropamida, Diabemide, Diabinese, Glucamide, Glymese, Melitase, NSC-44634, NSC-626720, chlorpropamide, SID11110918, SID11110919

Patent coverage: 10,383 distinct patent families (35,828 SureChEMBL compound mentions), from 1 matched compound structure(s). 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		0%	Q09428

Broader ChEMBL bioactivity targets: 13 (assay-derived). Sample: Survival motor neuron protein, Prelamin-A/C, Ferritin light chain, Solute carrier family 22 member 6, Thyroid hormone receptor beta, Thyrotropin receptor, 5-hydroxytryptamine receptor 2A, Alpha-1A adrenergic receptor, Nuclear factor NF-kappa-B p105 subunit, Cytochrome P450 3A4.

Bioactivity

ChEMBL activities: 14 potent at pChembl ≥ 5 of 19 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
LMNA	8.3	Potency	5	nM	CHEMBL_ACT_3645315
P02791	6.6	Potency	251.2	nM	CHEMBL_ACT_4480840
NFKB1	6.35	Potency	446.7	nM	CHEMBL_ACT_3671998
NFKB1	6.35	Potency	446.7	nM	CHEMBL_ACT_4585280
SMN1	5.8	Potency	1585	nM	CHEMBL_ACT_3890451
TSHR	5.8	Potency	1585	nM	CHEMBL_ACT_3936112
TSHR	5.8	Potency	1585	nM	CHEMBL_ACT_4735316
THRB	5.7	Potency	1995	nM	CHEMBL_ACT_4018793
TSHR	5.5	Potency	3162	nM	CHEMBL_ACT_3918009
TSHR	5.5	Potency	3162	nM	CHEMBL_ACT_4691145
NPSR1	5.3	Potency	5012	nM	CHEMBL_ACT_4908758
ADRA1A	5.24	AC50	5696	nM	CHEMBL_ACT_25137773
HTR2A	5.24	AC50	5818	nM	CHEMBL_ACT_25173522
ALDH1A1	5.1	Potency	7943	nM	CHEMBL_ACT_4192067

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

2 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

Clinical trials

Total trials: 1.

Phase distribution

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00004363	Not specified	COMPLETED	Study of the Pathogenesis and Pathophysiology of Familial Neurohypophyseal Diabetes Insipidus

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (1) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of CPIC Guideline for chlorpropamide, dabrafenib, gliclazid	CPIC	G6PD

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.

7 molecules share ≥1 primary target. Top 7 by shared-target count:

Molecule	Source	Status	Shared targets
DIAZOXIDE	ChEMBL + PubChem	Phase 4 (approved)	ABCC8
GLYBURIDE	ChEMBL + PubChem	Phase 4 (approved)	ABCC8
REPAGLINIDE	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