Pharmacological characterization of the selective 11ß-hydroxysteroid dehydrogenase 1 inhibitor, BI 135585, a clinical candidate for the treatment of type 2 diabetes.
Eur J Pharmacol
; 746: 50-5, 2015 Jan 05.
Article
en En
| MEDLINE
| ID: mdl-25445047
ABSTRACT
To combat the increased morbidity and mortality associated with the developing diabetes epidemic new therapeutic interventions are desirable. Inhibition of intracellular cortisol generation from cortisone by blocking 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) has been shown to ameliorate the risk factors associated with the metabolic syndrome. A challenge in developing 11ß-HSD1 inhibitors has been the species selectivity of small molecules, as many compounds are primate specific. Here we describe our strategy to identify potent selective 11ß-HSD1 inhibitors while ensuring target engagement in key metabolic tissues, liver and fat. This strategy enabled the identification of the clinical candidate, BI 135585.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_diabetes
/
6_endocrine_disorders
Asunto principal:
Oxazinas
/
Piridonas
/
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1
/
Diabetes Mellitus Tipo 2
/
Inhibidores Enzimáticos
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2015
Tipo del documento:
Article