CHLORPROPAMIDE

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H13ClN2O3S
Molecular Weight	276.74
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

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	276.74
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 13 Target ID: CHEMBL2096972 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22209866	Inhibitor 8297		3.04 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 259 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/011641s066lbl.pdf	Primary		Approved 8429	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 1958

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 1737 inhibitor 1587	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
PEPT1 20 PEPT2 10 BSEP 402 CYP51 2 MRP4 204 MRP2 383 MRP3 157 CYP1A2 1524 CYP2A6 707 CYP2C19 1478 CYP2E1 882 NTCP 34 OATP1B1 788 OATP1B3 706 P-gp 1461	CYP2C19 991 CYP1A2 1054 CYP2A6 543 CYP2C8 693 CYP2E1 667

Drug as perpetrator

Target	Modality	Activity
CYP2A6 739	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ5OCJ9fQ%3D%3D	no [IC50 >10 uM]
CYP2E1 970	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ5OCJ9fQ%3D%3D	no [IC50 >10 uM]
BSEP 403	inhibitor 3277 Sources: http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50344965, https://pubmed.ncbi.nlm.nih.gov/21965623/	no [IC50 >1000 uM]
MRP2 475	inhibitor 3277 Sources: http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50344965, https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP3 207	inhibitor 3277 Sources: http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50344965, https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP4 238	inhibitor 3277 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 3277 Sources: http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50344965	no [IC50 >200 uM]
OATP1B1 803	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ5OCJ9fQ%3D%3D	yes [Inhibition 10 uM]
OATP1B3 715	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ5OCJ9fQ%3D%3D	yes [Inhibition 10 uM]
NTCP 35	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1Mjg3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ5OCJ9fQ%3D%3D	yes [Inhibition 100 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22931300/	yes
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22931300/	yes
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22931300/	yes
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22931300/	yes
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22931300/	yes
P-gp 1650	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw0MzAyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ5OCJ9fQ%3D%3D	yes
PEPT1 22	inhibitor 3277 Sources: https://go.drugbank.com/drugs/DB00672, https://pubmed.ncbi.nlm.nih.gov/10748266/	yes
PEPT2 12	inhibitor 3277 Sources: https://go.drugbank.com/drugs/DB00672, https://pubmed.ncbi.nlm.nih.gov/10748266/	yes

Drug as victim

Target	Modality	Activity
CYP2C9 1037	substrate 3367 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 991	substrate 3367 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 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15842554/	minor
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15842554/	minor
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15842554/	minor
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15842554/	minor
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15842554/	minor
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15842554/	minor

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 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
Haemolysis and agranulocytosis complicating treatment with methyldopa.	1967 Oct 14	6047854
Pure red blood cell aplasia associated with chlorpropamide therapy. Patient summary and review of the literature.	1969 Apr	5781455
Chlorpropamide-induced immune hemolytic anemia.	1970 Oct 22	5458054
Severe hypoglycaemic shock caused by chlorpropamide. (Case report).	1971 Jan	5560028
Inappropriate secretion of antidiuretic hormone induced by chlorpropamide.	1972 Mar	5029389
Chlorpropamide and angina pectoris.	1973 Mar	4694904
[Case of hypoglycemic coma in a female patient with diabetes insipidus treated with chlorpropamide].	1974 Jan-Feb	4848193
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
Chlorpropamide-alcohol flushing: a dominantly inherited trait associated with diabetes.	1978 Dec 2	728707
Reduction of the severity of nephropathy in aging Fischer 344 rats treated with analogs of arylsulfonyluria.	1979 Jul	473209
Chlorpropamide induced syndrome of inappropriate antidiuretic hormone secretion.	1980 Apr	7218172
Tolazamide-induced cholestasis.	1980 Aug	7403921
Hypoglycemic coma, jaundice, and pure RBC aplasia following chlorpropamide therapy.	1980 May	7396601
Chlorpropamide-induced pure RBC aplasia.	1980 May	7396598
Megaloblastic anaemia due to vitamin B12 malabsorption associated with long-term metformin treatment.	1980 May 17	7388472
Chlorpropamide-induced haemolytic anaemia.	1981 Jan	7279824
Chlorpropamide-induced Syndrome of Inappropriate Antidiuretic Hormone Secretion.	1981 Jul	7240625
Chlorpropamide-induced optic neuropathy.	1982 Feb	7059267
Chlorpropamide-induced hypoglycemia. A dramatic presentation of celiac disease.	1982 Feb 12	7057563
Nephrotic syndrome and immune complex glomerulonephritis associated with chlorpropamide therapy.	1983 Feb	6218754
The effect of chlorpropamide hyponatremia on mental status in a nursing home population.	1983 May	6842150
Chlorpropamide-induced hemolytic anemia.	1984 Dec	6510223
Acute hemolytic anemia associated with a chlorpropamide-induced apparent auto-anti-Jka.	1984 May-Jun	6427987
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
Chlorpropamide or chlorpromazine?	1991 Jan 15	2043180
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
Correlating structure and function in ATP-sensitive K+ channels.	1998 Jul	9683320
Effect of pressure up to 5.5GPa on dry powder samples of chlorpropamide form-A.	2006 Dec 11	16920295
Inhibition by natural dietary substances of gastrointestinal absorption of starch and sucrose in rats 2. Subchronic studies.	2007 Aug 10	17713601
Inhibition by natural dietary substances of gastrointestinal absorption of starch and sucrose in rats and pigs: 1. Acute studies.	2007 Aug 6	17713600
A new gamma-polymorph of chlorpropamide: 4-chloro-N-(propylaminocarbonyl)benzenesulfonamide.	2007 Jun	17551203
Studying the human brain anatomical network via diffusion-weighted MRI and Graph Theory.	2008 Apr 15	18272400
Chlorpropamide treatment restores the reduced carrageenan-induced paw edema and pleural exudate volume in diabetic rats.	2008 Sep	18777112
A conformational polymorphic transition in the high-temperature epsilon-form of chlorpropamide on cooling: a new epsilon'-form.	2009 Dec	19923705
Comprehensive in silico prediction and analysis of chlamydial outer membrane proteins reflects evolution and life style of the Chlamydiae.	2009 Dec 29	20040079
Quantitative 35Cl nuclear quadrupole resonance in tablets of the antidiabetic medicine Diabinese.	2009 Jul 1	19492808
Metformin use and prostate cancer in Caucasian men: results from a population-based case-control study.	2009 Nov	19653109
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
Epac2: a sulfonylurea receptor?	2012 Feb	22260657
Pharmacogenomic analysis of ATP-sensitive potassium channels coexpressing the common type 2 diabetes risk variants E23K and S1369A.	2012 Mar	22209866
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 Dec 15 15:21:56 GMT 2023` Edited by `admin` on `Fri Dec 15 15:21:56 GMT 2023`
Record UNII	WTM2C3IL2X
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CHLORPROPAMIDE

Official Name

English

CHLORPROPAMIDE [EP IMPURITY]

Common Name

English

CHLORPROPAMIDE [USP-RS]

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 [WHO-DD]

Common 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