Design of Dimeric Bile Acid Derivatives as Potent and Selective Human NTCP Inhibitors.
J Med Chem
; 64(9): 5973-6007, 2021 05 13.
Article
em En
| MEDLINE
| ID: mdl-33906348
ABSTRACT
Dimeric bile acid derivatives (DBADs) were developed and tested for their anti-HBV and anti-HDV activities as sodium taurocholate cotransporting polypeptide (NTCP) inhibitors. DBADs exhibited strong and persistent potency of NTCP inhibition, whereas diverse linkers and constitutions showed distinct inhibition features. Motif aa157-165 on NTCP was shown to be a possible binding site of DBADs; therefore, we determined DBADs' selectivity among NTCPs from different species. A cyclized DBAD scaffold DBA-41 exhibited a high affinity to human NTCP (hNTCP). Intraperitoneal administration of DBA-41 to hNTCP-tg mice induced serum total bile acid elevation. DBA-41 may serve as a biological tool to study NTCP physiological function.
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Base de dados:
MEDLINE
Assunto principal:
Ácidos e Sais Biliares
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Desenho de Fármacos
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Dimerização
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Transportadores de Ânions Orgânicos Dependentes de Sódio
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Simportadores
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article