Glibenclamide

Names

[ Name ]:
Glibenclamide

[Synonym ]:
glybenzcyclamide
Glybenclamide
Daonil
MFCD00056625
5-Chloro-N-(2-{4-[(cyclohexylcarbamoyl)sulfamoyl]phenyl}ethyl)-2-methoxybenzamide
Benzamide, 5-chloro-N-[2-[4-[[[(cyclohexylamino)carbonyl]amino]sulfonyl]phenyl]ethyl]-2-methoxy-
Benzenecarboximidic acid, 5-chloro-N-[2-[4-[[[(E)-(cyclohexylimino)hydroxymethyl]amino]sulfonyl]phenyl]ethyl]-2-methoxy-
Glyburide
5-Chloro-N-[2-(4-{[(E)-(cyclohexylimino)(hydroxy)methyl]sulfamoyl}phenyl)ethyl]-2-methoxybenzenecarboximidic acid
Diabeta
Euglucon
Micronase
EINECS 233-570-6
5-Chloro-N-[4-(3-cyclohexylureidosulfonyl)phenethyl]-2-methoxybenzamide
Glynase
Glibenclamide
5-chloro-N-[2-[4-(cyclohexylcarbamoylsulfamoyl)phenyl]ethyl]-2-methoxybenzamide
5-Chloro-N-(4-(N-(cyclohexylcarbamoyl)sulfamoyl)phenethyl)-2-methoxybenzamide

Biological Activity

[Description]:

Glibenclamide(Glyburide) is a sulfonylurea compound that modulates insulin production. IC50 value:Target:Sulfonylureas bind to ATP-dependent K+ channels in beta cells of the pancreas, depolarizing them and stimulating the release of Ca2+, which in turn stimulates insulin production. Glibenclamide, a sulphonylurea oral hypoglycaemic agent is a widely used antagonist of cromakalim-activated K+ channels in smooth muscle. Binding of Gli to SUR produces the closure of KATP channels and the inhibition of their activity. Glibenclamide is widely used for treatment of type 2-diabetes and it has been signaled as antiproliferative in several tumor cell lines.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

Research Areas >> Metabolic Disease

[References]

[1]. Núnez M, Medina V, Cricco G, et al. Glibenclamide inhibits cell growth by inducing G0/G1 arrest in the human breast cancer cell line MDA-MB-231. BMC Pharmacol Toxicol. 2013 Jan 11;14(1):6.

[2]. Soydan N, Bretzel RG, Fischer B, et al. Reduced capacity of heart rate regulation in response to mild hypoglycemia induced by glibenclamide and physical exercise in type 2 diabetes. Metabolism. 2013 Jan 11. pii: S0026-0495(12)00456-8.

[3]. Sokolovska J, Isajevs S, Sugoka O, et al. Comparison of the Effects of Glibenclamide on Metabolic Parameters, GLUT1 Expression, and Liver Injury in Rats With Severe and Mild Streptozotocin-Induced Diabetes Mellitus. Medicina (Kaunas). 2012;48(10):532-43.

[4]. Gangji AS, Cukierman T, Gerstein HC et al. A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of glyburide with other secretagogues and with insulin. Diabetes Care. 2007 Feb;30(2):389-94.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
705.7±70.0 °C at 760 mmHg

[ Melting Point ]:
173-175°C

[ Molecular Formula ]:
C₂₃H₂₈ClN₃O₅S

[ Molecular Weight ]:
494.004

[ Flash Point ]:
380.6±35.7 °C

[ Exact Mass ]:
493.143829

[ PSA ]:
121.98000

[ LogP ]:
5.19

[ Vapour Pressure ]:
0.0±2.4 mmHg at 25°C

[ Index of Refraction ]:
1.623

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: YS4725200

CHEMICAL NAME :: Urea, 1-((p-(2-(chloro-o-anisamido)ethyl)phenyl)sulfonyl)-3 -cyclohexyl-

CAS REGISTRY NUMBER :: 10238-21-8

LAST UPDATED :: 199612

DATA ITEMS CITED :: 15

MOLECULAR FORMULA :: C23-H28-Cl-N3-O5-S

MOLECULAR WEIGHT :: 494.05

WISWESSER LINE NOTATION :: L6TJ AMVMSWR D2MVR EG BO1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 147 ug/kg

TOXIC EFFECTS :: Behavioral - coma Endocrine - hypoglycemia

REFERENCE :: DICPBB Drug Intelligence and Clinical Pharmacy. (POB 42435, Cincinnati, OH 45242) V.3- 1969- Volume(issue)/page/year: 18,142,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >20 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 19,1413,1969

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 3750 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 19,1413,1969

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >20 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 19,1413,1969

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 3250 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 16,1640,1966

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 5900 mg/kg

TOXIC EFFECTS :: Behavioral - changes in motor activity (specific assay) Skin and Appendages - hair Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,247,1970

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >20 gm/kg

TOXIC EFFECTS :: Skin and Appendages - dermatitis, other (after systemic exposure)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,247,1970

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >10 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 19,1404,1969

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: >20 gm/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,247,1970

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: >15 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 19,1404,1969 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 801 mg/kg/26W-I

TOXIC EFFECTS :: Liver - other changes Biochemical - Metabolism (Intermediary) - lipids including transport Related to Chronic Data - death

REFERENCE :: HEPHD2 Handbook of Experimental Pharmacology. (Springer-Verlag, Heidelberger Pl. 3, D-1000 Berlin 33, Fed. Rep. Ger.) V.50- 1978- Volume(issue)/page/year: 119,185,1996 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 20 mg/kg

SEX/DURATION :: female 6-15 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,271,1970

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 4 mg/kg

SEX/DURATION :: female 5-9 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive)

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 21,846,1971

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 1800 mg/kg

SEX/DURATION :: female 9-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :: SEIJBO Senten Ijo. Congenital Anomalies. (Nippon Senten Ijo Gakkai, c/o Kinki Daigaku Igakubu Kaibagaku Kyoshitsu, 380 Nishiyama, Sayama-cho, Mirami-Kawachi-gun, Osaka-fu, Japan) V.1-26, 1960-86. For publisher information, see CGANE7. Volume(issue)/page/year: 17,31,1977

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 180 mg/kg

SEX/DURATION :: female 9-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - eye/ear

REFERENCE :: SEIJBO Senten Ijo. Congenital Anomalies. (Nippon Senten Ijo Gakkai, c/o Kinki Daigaku Igakubu Kaibagaku Kyoshitsu, 380 Nishiyama, Sayama-cho, Mirami-Kawachi-gun, Osaka-fu, Japan) V.1-26, 1960-86. For publisher information, see CGANE7. Volume(issue)/page/year: 17,31,1977

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ Hazard Codes ]:
Xn

[ Risk Phrases ]:
R20/21/22

[ Safety Phrases ]:
S22-S36/37/39

[ RIDADR ]:
NONH for all modes of transport

[ RTECS ]:
YS4725200

[ HS Code ]:
2935009090

Customs

[ HS Code ]: 2935009090

[ Summary ]:
2935009090 other sulphonamides VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:35.0%

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