Aldose reductase structures: implications for mechanism and inhibition.
Cell Mol Life Sci
; 61(7-8): 750-62, 2004 Apr.
Article
en En
| MEDLINE
| ID: mdl-15095000
ABSTRACT
During chronic hyperglycaemia, elevated vascular glucose level causes increased flux through the polyol pathway, which induces functional and morphological changes associated with secondary diabetic complications. Inhibitors of aldose reductase (ARIs) have been widely investigated as potential therapeutic agents, but to date only epalrestat is successfully marketed for treatment of diabetic neuropathy, in Japan. Promising compounds during in vitro studies or in trials with animal models have failed to proceed beyond clinical trials and to everyday use, due to a lack of efficacy or adverse side effects attributed to lack of inhibitor specificity and likely inhibition of the related aldehyde reductase (ALR1). Knowledge of the catalytic mechanism and structures of the current inhibitors complexed with ALR2 are means by which more specific and tightly bound inhibitors can be discovered. This review will provide an overview of the proposed catalytic mechanism and the current state of structure-based drug design.
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Banco de datos:
MEDLINE
Asunto principal:
Rodanina
/
Aldehído Reductasa
/
Inhibidores Enzimáticos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Mol Life Sci
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2004
Tipo del documento:
Article
País de afiliación:
Australia