CHLORPROPAMIDE

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H13ClN2O3S
Molecular Weight	276.7412
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCN=C(NS(=O)(=O)c1ccc(cc1)Cl)O

InChI

InChIKey=RKWGIWYCVPQPMF-UHFFFAOYSA-N

InChI=1S/C10H13ClN2O3S/c1-2-7-12-10(14)13-17(15,16)9-5-3-8(11)4-6-9/h3-6H,2,7H2,1H3,(H2,12,13,14)

HIDE SMILES / InChI

Molecular Formula	C10H13ClN2O3S
Molecular Weight	276.7412
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/011641s066lbl.pdf
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/mesh/68002747

Chlorpropamide (DIABINESE®), is a sulfonylurea hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. It appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which chlorpropamide (DIABINESE®) lowers blood glucose during long-term administration has not been clearly established. Extra-pancreatic effects may play a part in the mechanism of action of oral sulfonylurea hypoglycemic drugs. While chlorpropamide is a sulfonamide derivative, it is devoid of antibacterial activity. Chlorpropamide (DIABINESE®) may also prove effective in controlling certain patients who have experienced primary or secondary failure to other sulfonylurea agent.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sulfonylurea receptor 1, Kir6.2 12 Target ID: CHEMBL2096972 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22209866	Inhibitor 7728		3.04 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 240 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/011641s066lbl.pdf	Primary		Approved 8043	DIABINESE Approved Use Chlorpropamide tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Launch Date -3.52771211E11

C_max

Value	Dose	Co-administered	Analyte	Population
28.5 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/5053812/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORPROPAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
545 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/5053812/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORPROPAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
33.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/5053812/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORPROPAMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1601 inhibitor 1467	substrate 936 inhibitor 1604	substrate 1118 inhibitor 1702	inhibitor 1475

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
PEPT1 19 PEPT2 9 BSEP 376 CYP51 2 MRP4 194 MRP2 346 MRP3 150 CYP1A2 1383 CYP2A6 627 CYP2C19 1325 CYP2E1 790 NTCP 32 OATP1B1 733 OATP1B3 657 P-gp 1330	CYP2C19 910 CYP1A2 972 CYP2A6 485 CYP2C8 634 CYP2E1 606

Drug as perpetrator

Target	Modality	Activity
CYP2A6 659	inhibitor 3045 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ5OCJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2E1 871	inhibitor 3045 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ5OCJ9fQ%3D%3D	no [IC50 >10 uM]
BSEP 377	inhibitor 3045 Sources: http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50344965, https://pubmed.ncbi.nlm.nih.gov/21965623/	no [IC50 >1000 uM]
MRP2 434	inhibitor 3045 Sources: http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50344965, https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP3 200	inhibitor 3045 Sources: http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50344965, https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP4 226	inhibitor 3045 Sources: http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50344965, https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
CYP51 2	inhibitor 3045 Sources: http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50344965	no [IC50 >200 uM]
OATP1B1 748	inhibitor 3045 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ5OCJ9fQ%3D%3D	yes [Inhibition 10 uM]
OATP1B3 666	inhibitor 3045 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ5OCJ9fQ%3D%3D	yes [Inhibition 10 uM]
NTCP 33	inhibitor 3045 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1Mjg3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ5OCJ9fQ%3D%3D	yes [Inhibition 100 uM]
CYP1A2 1532	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/22931300/	yes
CYP2C19 1392	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/22931300/	yes
CYP2C9 1648	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/22931300/	yes
CYP2D6 1738	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/22931300/	yes
CYP3A4 1772	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/22931300/	yes
P-gp 1514	inhibitor 3045 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw0MzAyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ5OCJ9fQ%3D%3D	yes
PEPT1 21	inhibitor 3045 Sources: https://go.drugbank.com/drugs/DB00672, https://pubmed.ncbi.nlm.nih.gov/10748266/	yes
PEPT2 11	inhibitor 3045 Sources: https://go.drugbank.com/drugs/DB00672, https://pubmed.ncbi.nlm.nih.gov/10748266/	yes

Drug as victim

Target	Modality	Activity
CYP2C9 936	substrate 3113 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000094202, https://pubmed.ncbi.nlm.nih.gov/15842554/	major [Km 249.6 uM]
CYP2C19 910	substrate 3113 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000094202, https://pubmed.ncbi.nlm.nih.gov/15842554/	major [Km 584.9 uM]
CYP1A2 972	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/15842554/	minor
CYP2A6 485	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/15842554/	minor
CYP2C8 634	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/15842554/	minor
CYP2D6 1118	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/15842554/	minor
CYP2E1 606	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/15842554/	minor
CYP3A4 1601	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/15842554/	minor

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1507	inhibitor 1489 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNDk4In19

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3650	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3650
ChemicalBook	CB8677954	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8677954
MolPort	MolPort-001-779-601	https://www.molport.com/shop/molecule-link/MolPort-001-779-601
Selleck Chemicals	chlorpropamide	http://www.selleckchem.com/products/chlorpropamide.html
ZINC	ZINC000001530599	http://zinc15.docking.org/substances/ZINC000001530599
eMolecules	535781	https://www.emolecules.com/cgi-bin/more?vid=535781

PubMed

Title	Date	PubMed
Encephalopathy induced by oral hypoglycemic drugs.	1977 Aug	879949
Chlorpropamide-alcohol flushing: a definition of its relation to non-insulin-dependent diabetes.	1978 Dec 2	728708
Tolazamide-induced cholestasis.	1980 Aug	7403921
Megaloblastic anaemia due to vitamin B12 malabsorption associated with long-term metformin treatment.	1980 May 17	7388472
Incidence of severe sideeffects during therapy with sulfonylureas and biguanides.	1985	3865878
A case of chronic liver disease due to tolazamide.	1985 Jul	4007403
Chlorpropamide-induced cholestatic jaundice and pseudomembranous colitis.	1985 May	2859803
The mechanisms of sulfonylurea-induced immune hemolysis: case report and review of the literature.	1986 Nov	3766527
Prolonged cholestasis and disappearance of interlobular bile ducts following chlorpropamide and erythromycin ethylsuccinate. Case of drug interaction?	1988 Dec	3265170
Chlorpropamide induced syndrome of inappropriate secretion of antidiuretic hormone.	1991 Aug	1814884
Hypertension secondary to chlorpropamide with amelioration by changing to insulin.	1993 Apr	8507452
Chlorpropamide-induced ADH release, hyponatremia and central pontine myelinolysis in diabetes mellitus.	1995 Dec	8928190
Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor.	1995 Nov 17	7502040
Chlorpropamide-induced cholestatic liver failure resulting in death.	1996 May-Jun	15251538
Correlating structure and function in ATP-sensitive K+ channels.	1998 Jul	9683320
[Hepatotoxic reaction associated with metformin and chlorpropamide treatment].	1999 Feb	10216414
Studying the human brain anatomical network via diffusion-weighted MRI and Graph Theory.	2008 Apr 15	18272400
Maitake mushroom extracts ameliorate progressive hypertension and other chronic metabolic perturbations in aging female rats.	2010 Jun 7	20567593
Ameliorative effects of Cnidoscolus aconitifolius on alloxan toxicity in Wistar rats.	2010 Sep	21327141
A correlation between the in vitro drug toxicity of drugs to cell lines that express human P450s and their propensity to cause liver injury in humans.	2014 Jan	24085192

Patents

Sample Use Guides

In Vivo Use Guide

The mild to moderately severe, middle-aged, stable type 2 diabetes patient should be started on 250 mg daily. In elderly patients, debilitated or malnourished patients, and patients with impaired renal or hepatic function, the initial and maintenance dosing should be conservative to avoid hypoglycemic reactions. Older patients should be started on smaller amounts of DIABINESE®, in the range of 100 to 125 mg daily.

Route of Administration: Oral

In Vitro Use Guide

The ATP-sensitive potassium channels containing the K23/A1369 risk haplotype were significantly less sensitive to inhibition by chlorpropamide (IC50 values for risk haplotype K23/A1369 vs. nonrisk haplotype E23/S1369 = 4.19 vs. 3.04 uM).

Substance Class	Chemical Created by `admin` on `Fri Jun 25 20:57:38 UTC 2021` Edited by `admin` on `Fri Jun 25 20:57:38 UTC 2021`
Record UNII	WTM2C3IL2X
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CHLORPROPAMIDE

Official Name

English

CHLORPROPAMIDE [EP]

Common Name

English

CHLORPROPAMIDE [USP-RS]

Common Name

English

CHLORPROPAMIDE [WHO-DD]

Common Name

English

CHLORPROPAMIDE [MI]

Common Name

English

GLUCAMIDE

Brand Name

English

CHLORPROPAMIDE [HSDB]

Common Name

English

CHLORPROPAMIDE [INN]

Common Name

English

CHLORPROPAMIDE [ORANGE BOOK]

Common Name

English

NSC-44634

Code

English

CHLORPROPAMIDE [MART.]

Common Name

English

BENZENESULFONAMIDE, 4-CHLORO-N-((PROPYLAMINO)CARBONYL)-

Systematic Name

English

CHLORPROPAMIDE [JAN]

Common Name

English

1-((P-CHLOROPHENYL)SULFONYL)-3-PROPYLUREA

Common Name

English

DIABINESE

Brand Name

English

CHLORPROPAMIDE [VANDF]

Common Name

English

NSC-626720

Code

English

CHLORPROPAMIDE [USP MONOGRAPH]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QA10BB02