Nicotinic acids: liver-targeted SCD inhibitors with preclinical anti-diabetic efficacy.
Bioorg Med Chem Lett
; 21(24): 7281-6, 2011 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-22047692
ABSTRACT
An in vitro screening protocol was used to transform a systemically-distributed SCD inhibitor into a liver-targeted compound. Incorporation of a key nicotinic acid moiety enables molecular recognition by OATP transporters, as demonstrated by uptake studies in transfected cell lines, and likely serves as a critical component of the observed liver-targeted tissue distribution profile. Preclinical anti-diabetic oGTT efficacy is demonstrated with nicotinic acid-based, liver-targeting SCD inhibitor 10, and studies with a close-structural analog devoid of SCD1 activity, suggest this efficacy is a result of on-target activity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estearoil-CoA Dessaturase
/
Inibidores Enzimáticos
/
Hipoglicemiantes
/
Ácidos Nicotínicos
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article