Suchergebnisse

World-wide introduction of high throughput screening (HTS) methods in
drug discovery research did not result in the increased number of novel medications on
the market. We discuss novel trends in drug discovery that came from the understanding
that majority of diseases are multifactorial and that one enzyme has many protein
substrates. Hence, new approaches are focused on development of drugs, which (1)
trigger survival pathways to return the organism to homeostatic balance, and (2)
inhibit enzymes modifying histones or transcription factors not at the active site, but
by displacement of protein substrates from the enzyme complexes. A good example
for both approaches comes from the development of activators of antioxidant defense.
We analyze and illustrate problems of commonly used in vitro HTS assays, and briefl y
discuss advantages and limitations of small animal models. The novel approaches are
complementary to the standard HTS and do not substitute for testing in mammals.
Development of transgenic reporter mice to monitor drug effects by means of in vivo
imaging is extremely promising to select proper dosage and administration regimes for
full-range PK studies.