Benfluorex hydrochloride

[Description]:

Benfluorex hydrochloride (JP-992 hydrochloride) is a hepatic nuclear factor 4 alpha (HNF4α) activator.

[Related Catalog]:

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Others >> Others

Research Areas >> Metabolic Disease

[Target]

HNF4α[1]

[In Vitro]

Benfluorex hydrochloride consistently activates insulin promoter activity as measured by an increased number of GFP-positive cells. Benfluorex hydrochloride increases the number of GFP-positive cells in a dose-responsive manner and increases the level of endogenous insulin mRNA. Consistent with being HNF4α activator, Benfluorex hydrochloride stimulates HNF4α expression. Benfluorex hydrochloride alters HNF4α protease sensitivity, while the inactive control compound does not[1]. Benfluorex hydrochloride decreases, in a concentration-dependent manner, the synthesis of acid-soluble products and ketone bodies from oleate, whereas the production of 14CO2 into citric acid cycle is markedly increased by Benfluorex hydrochloride. Benfluorex hydrochloride inhibits in a dose-dependent manner the rates of gluconeogenesis from lactate/pyruvate (10/1 nM)[2].

[Kinase Assay]

HepG2 cells are treated with DMSO or Benfluorex hydrochloride at a concentration of 20 µM or 40 µM for 16 hr.Total cell protein is extracted, measured by BCA protein assay. Each sample is split into two aliquots for proteolysis without (-) or with (+) Subtilisin. Twenty ug of cell lysate is incubated with or without protease (20 ng/mL subtilisin) for 35 minutes at room temperature. Western blot is then performed with primary anti-HNF4α polyclonal antibody (1:1000 dilution) and secondary HRP conjugated anti-goat IgG (1:2000 dilution), detected with chemiluminescence ECL kit[1].

[Cell Assay]

Hepatocytes are isolated by in situ perfusion of the liver with 0.025% collagenase. Hepatocytes (1 to 2×106 cells/mL) are incubated at 37°C in 2 mL of oxygenated (O2:CO2; 95:5) Krebs-Henseleit bicarbonate buffer (pH 7.4) for 1 h in a gyratory shaking water bath. Benfluorex hydrochloride is dissolved in DMSO and added (10 μL) to the incubation medium at a final concentration of 0.1 or 1 nM[2].

[References]

[1]. Lee SH, et al. Identification of alverine and benfluorex as HNF4α activators. ACS Chem Biol. 2013 Aug 16;8(8):1730-6.

[2]. Kohl C, et al. Effects of benfluorex on fatty acid and glucose metabolism in isolated rat hepatocytes: from metabolic fluxes to gene expression. Diabetes. 2002 Aug;51(8):2363-8.

[ Density]:
1.183g/cm3

[ Boiling Point ]:
420.5ºC at 760mmHg

[ Melting Point ]:
158-159?C

[ Molecular Formula ]:
C₁₉H₂₁ClF₃NO₂

[ Molecular Weight ]:
387.82400

[ Flash Point ]:
208.1ºC

[ Exact Mass ]:
387.12100

[ PSA ]:
38.33000

[ LogP ]:
5.27590

[ Vapour Pressure ]:
2.81E-07mmHg at 25°C

[ Storage condition ]:
Refrigerator

Click to get detail MSDS

CHEMICAL IDENTIFICATION

RTECS NUMBER :: KL8526000

CHEMICAL NAME :: Ethanol, 2-((1-methyl-2-(3-(trifluoromethyl)phenyl)ethyl)amino )-, benzoate (ester), hydrochloride

CAS REGISTRY NUMBER :: 23642-66-2

LAST UPDATED :: 199509

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C19-H20-F3-N-O2.Cl-H

MOLECULAR WEIGHT :: 387.86

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 108 mg/kg

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

REFERENCE :: AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 195,252,1972

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

[ Hazard Codes ]:
Xi: Irritant;

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
2

[ RTECS ]:
KL8275000

[Benfluorex and valvular heart disease].

Presse Med. 40(11) , 1008-16, (2011)

Benfluorex is responsible of restrictive organic valvular regurgitations via one of its metabolites, the norfenfluramine. It has been withdrawn from the european market in June 2010. In France, about ...

[About the settlement of litigations concerning the harm caused by benfluorex (Mediator®)].

Presse Med. 42(4 Pt 1) , 411-8, (2013)

Since September 1st 2011, the National Bureau for Compensation of Medical Accidents represents a unique portal for out-of-court settlement of litigations concerning the harm caused by benfluorex. In D...

[Reform Act on safety of drug and health products in France: announcement effect, strengthening or upheaval?].

Therapie. 67(1) , 1-10, (2012)

In France, the Médiator(®) scandal and the trauma it has created, are the source of Law n° 2011-2012 of 29 December 2011 on strengthening safety of drug and health products, intended by the Ministry o...

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