Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Más filtros

Banco de datos
Tipo del documento
Intervalo de año de publicación
1.
Bioorg Med Chem Lett ; 18(16): 4723-6, 2008 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-18676144

RESUMEN

Tie-2 is a receptor tyrosine kinase which is involved in angiogenesis and thereby growth of human tumours. The discovery and SAR of a novel class of imidazole-vinyl-pyrimidine kinase inhibitors, which inhibit Tie-2 in vitro is reported. Their synthesis was carried out by condensation of imidazole aldehydes with methyl pyrimidines. These compounds are lead-like, with low molecular weight, good physical properties and oral bioavailability.


Asunto(s)
Imidazoles/síntesis química , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/síntesis química , Pirimidinas/farmacología , Receptor TIE-2/antagonistas & inhibidores , Administración Oral , Disponibilidad Biológica , Química Farmacéutica/métodos , Diseño de Fármacos , Humanos , Imidazoles/administración & dosificación , Concentración 50 Inhibidora , Modelos Químicos , Conformación Molecular , Neovascularización Patológica , Inhibidores de Proteínas Quinasas/administración & dosificación , Pirimidinas/administración & dosificación , Receptor TIE-2/química , Relación Estructura-Actividad
2.
J Biomol Screen ; 21(2): 111-6, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26586251

RESUMEN

The fatty acid synthase (FAS) enzyme in mammalian cells is a large multidomain protein responsible for de novo synthesis of fatty acids. The steps catalyzed by FAS involve the condensation of acetyl-CoA and malonyl-CoA moieties in the presence of NADPH until palmitate is formed. Inhibition of FAS causes an accumulation of intracellular malonyl-CoA, as this metabolite is essentially committed to fatty acid synthesis once formed. Detection of intracellular metabolites for screening can be problematic due to a lack of appropriate tools, but here we describe a targeted liquid chromatography-mass spectroscopy (LCMS) method to directly measure endogenous levels of malonyl-CoA to drive a drug development structure-activity relationship (SAR) screening cascade. Our process involves preparation of samples at 96-well scale, normalization postpermeabilization via use of a whole-well imaging platform, and the LCMS detection methodology. The assay is amenable to multiplexing cellular endpoints, has a typical Z' of >0.6, and has high reproducibility of EC50 values.


Asunto(s)
Bioensayo/métodos , Cromatografía Liquida/métodos , Inhibidores Enzimáticos/química , Ácido Graso Sintasas/antagonistas & inhibidores , Malonil Coenzima A/química , Espectrometría de Masas/métodos , Línea Celular Tumoral , Ácidos Grasos/química , Humanos , NADP/química , Relación Estructura-Actividad , Especificidad por Sustrato
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA