Two approaches to discovering and developing new drugs for Chagas disease
Mem. Inst. Oswaldo Cruz
; 104(supl.1): 263-269, July 2009. tab
Artigo
em Inglês
| LILACS
| ID: lil-520888
Biblioteca responsável:
BR1.1
ABSTRACT
This review will focus on two general approaches carried out at the Sandler Center, University of California, San Francisco, to address the challenge of developing new drugs for the treatment of Chagas disease. The first approach is target-based drug discovery, and two specific targets, cytochrome P450 CYP51 and cruzain (aka cruzipain), are discussed. A "proof of concept" molecule, the vinyl sulfone inhibitor K777, is now a clinical candidate. The preclinical assessment compliance for filing as an Investigational New Drug with the United States Food and Drug Administration (FDA) is presented, and an outline of potential clinical trials is given. The second approach to identifying new drug leads is parasite phenotypic screens in culture. The development of an assay allowing high throughput screening of Trypanosoma cruzi amastigotes in skeletal muscle cells is presented. This screen has the advantage of not requiring specific strains of parasites, so it could be used with field isolates, drug resistant strains or laboratory strains. It is optimized for robotic liquid handling and has been validated through a screen of a library of FDA-approved drugs identifying 65 hits.
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Contexto em Saúde:
ODS3 - Saúde e Bem-Estar
/
Doenças Negligenciadas
Problema de saúde:
Meta 3.3: Acabar com as doenças tropicais negligenciadas e combater as doenças transmissíveis
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Doença de Chagas
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Doenças Negligenciadas
Base de dados:
LILACS
Assunto principal:
Tripanossomicidas
/
Compostos de Vinila
/
Desenho de Fármacos
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Inibidores de Cisteína Proteinase
/
Doença de Chagas
/
Dipeptídeos
Limite:
Animais
/
Humanos
País/Região como assunto:
América do Norte
Idioma:
Inglês
Revista:
Mem. Inst. Oswaldo Cruz
Assunto da revista:
Medicina Tropical
/
Parasitologia
Ano de publicação:
2009
Tipo de documento:
Artigo
/
Documento de projeto
País de afiliação:
Estados Unidos
Instituição/País de afiliação:
University of California/US