Characterization of hit molecules identified by high throughput screening (HTS) is an essential part of drug discovery.  Hundreds to thousands of hit molecules must be characterized by secondary screens, which are not always amendable to a higher throughput format.  Herein, we present the development of a HTS assay that enables the identification of reactive electrophilic small molecules.  Thiol-containing molecules have an essential role in many biochemical and physiological reactions due to the ease of which they are oxidized.  Glutathione is the most abundant non-protein thiol as it is found in the millimolar range in most cells.  Therefore, it is important to determine the reactivity of the small molecules with thiols to circumvent compound depletion.  Currently, there are no established pre-clinical high throughput assays for the assessment of compound reactivity towards glutathione.  With the use of intrinsically fluorescent thiol-containing molecules, the binding ability can be sensitively and selectively determined.

High throughput determination of glutathione binding ability of small molecules with the use of intrinsically fluorescent probes

243rd National Meeting (2012)

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