Biomedical Engineering Reference
In-Depth Information
of several thousand compounds. Migration, invasion, cell motility, and chemotaxis
assays have been used routinely in basic research for decades. Special assay plates
and screening approaches have been developed and are now commercially available
to enable use of these assays in a medium-throughput format. Most of these assays
are more robust when used with image-based screening, but some can also be opti-
mized successfully for use with plate readers. While such complex functional assays
are very useful for evaluation of DOS compound effects, it is often very difficult
to decipher their mechanism of action, due to the large number of cellular compo-
nents, signaling events, and pathways involved in complex biological behavior such
as cell movement. For such projects to succeed, a good strategy for target or MOA
deconvolution is critical.
12.4 FUTURE PERSPECTIVES
DOS compound collections provide an unprecedented level of chemical diversity. In
addition to traditional target- and mechanism-based screening approaches, they could
benefit significantly from utilization of mechanism-agnostic and phenotypic assays.
Holding their promise, DOS collections are likely to lead to the identification of new
target classes or the discovery of novel modulation mechanisms for difficult targets.
Utilization of qHTS and mHTS screening modalities may be particularly attractive,
as they allow rapid profiling and characterization of compounds and are especially
beneficial for small compound collections.
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