An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits.
Science
; 282(5389): 751-4, 1998 Oct 23.
Article
em En
| MEDLINE
| ID: mdl-9784135
ABSTRACT
Patients with abetalipoproteinemia, a disease caused by defects in the microsomal triglyceride transfer protein (MTP), do not produce apolipoprotein B-containing lipoproteins. It was hypothesized that small molecule inhibitors of MTP would prevent the assembly and secretion of these atherogenic lipoproteins. To test this hypothesis, two compounds identified in a high-throughput screen for MTP inhibitors were used to direct the synthesis of a highly potent MTP inhibitor. This molecule (compound 9) inhibited the production of lipoprotein particles in rodent models and normalized plasma lipoprotein levels in Watanabe-heritable hyperlipidemic (WHHL) rabbits, which are a model for human homozygous familial hypercholesterolemia. These results suggest that compound 9, or derivatives thereof, has potential applications for the therapeutic lowering of atherogenic lipoprotein levels in humans.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apolipoproteínas B
/
Piperidinas
/
Triglicerídeos
/
Proteínas de Transporte
/
Colesterol
/
Fluorenos
/
Hiperlipoproteinemia Tipo II
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
1998
Tipo de documento:
Article