Carnitine palmitoyltransferase (CPT) modulators: A medicinal chemistry perspective on 35 years of research

Journal of Medicinal Chemistry

Volumn 54, Issue 9, 2011, Pages 3109-3152

  Ceccarelli, Simona M ^a   Chomienne, Odile ^a   Gubler, Marcel ^a   Arduini, Arduino ^b  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

^b Tecnopolo ^*  (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

2 [5 (4 CHLOROPHENYL)PENTYL]OXIRANE 2 CARBOXYLATE COENZYME A; 2 [5 (4 CHLOROPHENYL)PENTYL]OXIRANE 2 CARBOXYLATE ETHYL ESTER; 2 TETRADECYLGLYCIDIC ACID COENZYME A; ACETYLAMINOCARNITINE; CARNITINE DERIVATIVE; CARNITINE PALMITOYLTRANSFERASE; CARNITINE PALMITOYLTRANSFERASE INHIBITOR; CLOMOXIR; DECHLOROETOMOXIR COENZYME A; EMERIAMINE; EMERICEDIN; ETOMOXIR; ETOMOXIR COENZYME A; ETOMOXIR ETHYL ESTER; HEMIPALMITOYLCARNITINIUM; MYRISTOYLAMINOCARNITINE; NICOTINIC ACID; OCTANOYLCARNITINE; OXALIC ACID DERIVATIVE; OXIRANE CARBOXYLIC ACID DERIVATIVE; PALMITOYLAMINOCARNITINE; PALMOXIRIC ACID; PALMOXIRIC ACID METHYL ESTER; PERHEXILINE; SDZ CPI 975; ST 2425; ST 2452; TEGLICAR; TRIMETAZIDINE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ARTICLE; CENTRAL NERVOUS SYSTEM; CONGESTIVE HEART FAILURE; DIABETIC KETOACIDOSIS; DOSE RESPONSE; DRUG DELIVERY SYSTEM; DRUG POTENTIATION; DRUG SAFETY; DRUG STRUCTURE; ENERGY METABOLISM; ENZYME ACTIVE SITE; ENZYME DEFICIENCY; ENZYME INHIBITION; ENZYME STRUCTURE; HUMAN; INSULIN RESISTANCE; LOW DRUG DOSE; MITOCHONDRIAL MEMBRANE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; NUCLEOTIDE SEQUENCE; TISSUE DISTRIBUTION;

ANIMALS; CARNITINE; CARNITINE O-PALMITOYLTRANSFERASE; CATALYTIC DOMAIN; DIABETES MELLITUS, TYPE 2; ENERGY METABOLISM; ENZYME ACTIVATORS; ETHYLENE OXIDE; HEART FAILURE; HUMANS; INSULIN RESISTANCE; ISOENZYMES; LIPID METABOLISM; MYOCARDIAL ISCHEMIA; ORGAN SPECIFICITY; PROTEIN CONFORMATION; SEQUENCE HOMOLOGY, AMINO ACID; STEREOISOMERISM;

EID: 79955826359     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm100809g     Document Type: Article

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212. -1. The assay buffer contained 120 mM KCl, 25 mM Tris, pH 7.4, and 1 mM EDTA.
213. KB production was measured with cultured primary rat hepatocytes. Hepatocytes were isolated from fed normal Wistar rats by the liver collagenase-perfusion method. The cells were seeded in 24-well collagen-coated cell culture plates (250-000 cells per well) in RPMI 1640 medium without glucose containing 10% fetal bovine serum and 0.4% gentamycin, and the plates were incubated for 16 h at 37 °C. Medium was removed, and the cells were washed once with phosphate-buffered saline (PBS). Then 500 μL of fresh PBS containing 0.13% FA-free bovine serum albumin, 100 μM oleate, serial dilutions of CPT inhibitors, and DMSO up to 0.1% were added to the cells in each well, and incubation was continued for 6 h at 37 °C. At the end of the incubation, cell culture supernatants were collected and centrifuged and 40 μL samples were used for KB determination with a commercially available kit (Autokit 3-HB from Wako).
214. 2 released during palmitate oxidation was captured by the alkaline scintillant in the LumaPlate, and after termination of the incubation, the sandwich was disassembled and the radioactivity in the LumaPlates was counted on a TopCount β counter (PerkinElmer).
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