Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Biosci Rep ; 37(3)2017 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-28592559

RESUMO

Prolyl hydroxylases (PHDs) down-regulate the level of hypoxia-inducible factors (HIFs) by hydroxylating key proline residues that trigger the degradation of the protein and affect the cell and its ability to respond to hypoxic stress. Several small molecule PHD inhibitors are now in various preclinical and clinical stages for the treatment of anemia. The present study provides a detail kinetic analysis for some of these inhibitors. The data generated in the present study suggest that these compounds are reversible and compete directly with the co-substrate, 2-oxoglutarate (2-OG) for binding at the enzyme active site. Most of these compounds are pan PHD inhibitors and exhibit a time-dependent inhibition (TDI) mechanism due to an extremely slow dissociation rate constant, koff, and a long residence time.


Assuntos
Inibidores Enzimáticos/farmacologia , Prolina Dioxigenases do Fator Induzível por Hipóxia/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/farmacologia , Domínio Catalítico , Inibidores Enzimáticos/química , Humanos , Prolina Dioxigenases do Fator Induzível por Hipóxia/química , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Ácidos Cetoglutáricos/metabolismo , Cinética , Ligação Proteica , Bibliotecas de Moléculas Pequenas/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...