Carbenoxolone

Carbenoxolone, a semi-synthetic derivative of glycyrrhetinic acid, has previously been used for the management of dyspepsia and peptic ulcer because of its anti-inflammatory properties[3]. Carbenoxolone, a general hemichannel and gap junction inhibitor, has the therapeutic potential of carbenoxolone in the treatment of chronic liver disease[2]. Carbenoxolone is a suitable candidate for the inhibition of Aβ42 aggregation and the therapeutic potential of Cbx against AD[1]. Carbenoxolone is small molecule Pannexin1 (Panx1,is an ATP release channel) inhibitor, attenuate Panx1 channel activity through modulation of the first extracellular loop[4].Carbenoxolone is an 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor that converts inactive glucocorticoid into an active form. Carbenoxolone has antiviral activity against DENV infection targeting the virus itself[6].

Research Areas >> Infection

Research Areas >> Inflammation/Immunology

Research Areas >> Neurological Disease

[1]. Sharma S, et al. Inhibition of Alzheimer's amyloid-beta aggregation in-vitro by carbenoxolone:Insight into mechanism of action. Neurochem Int. 2017 Sep;108:481-493.

[2]. Crespo Yanguas S, et al. TAT-Gap19 and Carbenoxolone Alleviate Liver Fibrosis in Mice. Int J Mol Sci. 2018 Mar 12;19(3). pii: E817.

[3]. Hirata K, et al. Formulation of carbenoxolone for delivery to the skin. Int J Pharm. 2013 May 20;448(2):360-5.

[4]. Michalski K, et al. Carbenoxolone inhibits Pannexin1 channels through interactions in the first extracellular loop. J Gen Physiol. 2016 Feb;147(2):165-74.

[5]. Kim J, et al. Protective effect of carbenoxolone on ER stress-induced cell death in hypothalamic neurons. Biochem Biophys Res Commun. 2015 Dec 25;468(4):793-9.

[6]. Pu J, et al. Antiviral activity of Carbenoxolone disodium against dengue virus infection. J Med Virol. 2017 Apr;89(4):571-581

MOLECULAR FORMULA :

C34-H50-O7

MOLECULAR WEIGHT :

570.84

WISWESSER LINE NOTATION :

L F6 E6 B666 CV DUTJ A1 HVQ H1 K1 N1 O1 S1 S1 TOV2VQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

120 mg/kg/56D-I

TOXIC EFFECTS :

Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - muscle weakness

REFERENCE :

BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 2,150,1976

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2450 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 19,323,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

128 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 19,323,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1720 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 19,323,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1400 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #4224327

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

290 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #4363816

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

1060 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 19,323,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

371 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 19,323,1980 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1313 mg/kg

SEX/DURATION :

female 1-21 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Newborn - biochemical and metabolic

REFERENCE :

DBTGAJ Diabetologia. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.1- 1965- Volume(issue)/page/year: 39,1299,1996