Biological assay challenges from compound solubility: strategies for bioassay optimization.
Drug Discov Today
; 11(9-10): 446-51, 2006 May.
Article
em En
| MEDLINE
| ID: mdl-16635808
ABSTRACT
Compound solubility in buffers and dimethyl sulfoxide (DMSO) has emerged as an important issue. Many discovery compounds have low solubility but are potentially valuable as leads. Unfortunately, low solubility affects bioassays by causing underestimated activity, reduced HTS-hit rates, variable data, inaccurate SAR, discrepancies between enzyme and cell assays and inaccurate in vitro ADME-Tox testing. Strategies for optimizing bioassays include considering solubility in HTS-library design; early screening for solubility; improving storage and handling of DMSO stocks; optimizing dilution protocols; and ensuring that low-solubility compounds are fully solubilized in bioassays. These approaches allow for adequate assessments of valuable pharmacophores for which solubility can be chemically optimized at a later date.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Solventes
/
Bioensaio
/
Preparações Farmacêuticas
/
Dimetil Sulfóxido
Idioma:
En
Revista:
Drug Discov Today
Assunto da revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos