Overview of P-glycoprotein inhibitors: a rational outlook

Glicoproteina-p (P-gp), uma glicoproteina de transmembrana permeavel, e um membro da superfamilia (ABC) de cassete de gene de ligacao de ATP que funciona especificamente como um carreador mediado pelo transportador de efluxo ativo primario. E amplamente distribuido por todo o corpo e apresenta uma gama diversificada de substratos. Diversos agentes terapeuticos vitais sao substratos para P-gp e sua biodisponibilidade e reduzida ou a resistencia e induzida devido ao efluxo de proteinas. Portanto, os inibidores da P-gp foram explorados para a superacao da resistencia a multiplas drogas e problemas de biodisponibilidade deficiente dos substratos terapeuticos da P-gp. A sensibilidade das moleculas da droga a P-gp e vice-versa, pode ser estabelecida por varios modelos experimentais in silico, in vitro e in vivo. Desde a descoberta da P-gp, diversas pesquisas identificaram varias estruturas quimicas como inibidores da P-gp. O objetivo deste presente estudo foi o de enfatizar a descoberta e desenvolvimento de inibidores mais novos, inertes, atoxicos e mais eficazes, visando especificamente os da P-gp, como aqueles entre os extratos vegetais, excipientes e formulacoes farmaceuticas, e outras moleculas racionais de droga. As aplicacoes do conhecimento de biologia celular e molecular, bancos de dados estruturais in silico, estudos de modelagem molecular e analises da relacao quantitativa estrutura-atividade (QSAR) no desenvolvimento de novos inibidores racionais da P-gp tambem foram mencionados.

• Publication year

  2012

• Venue

  Brazilian Journal of Pharmaceutical Sciences

• Publication date

  2012-09-01

• Fields of study

  Not labeled

• Identifiers
  DOI 10.1590/S1984-82502012000300002
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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