Episphere™ is a suite of quantitative proteomics technologies for the discovery of drug candidates for epigenetic targets. With Episphere™, epigenetic targets can be screened in their native environment as part of their protein complexes.
In epigenetic drug discovery, poor understanding of how inhibitors act, and how selective they are for their target and its different protein complexes, is a big hurdle. Episphere™ addresses these hurdles to provide more effective and better characterised inhibitors.
Episphere™ technology can:
- Measure the interaction of drugs with epigenetic targets directly in cells and tissues.
- Distinguish between complexes in which epigenetic targets operate.
- Monitor the effects of a drug on the 'epigenetic signature' in cells and tissues.
Episphere™ advantages:
- Inhibition data is produced with native enzymes without the need for recombinant protein or any other artificial labelling. Recombinant assay systems have been found to often be unreliable for epigenetic enzymes.
- Epigenetic targets operate in large protein complexes, which determine cellular function and activity of epigenetic enzymes. The complexes are therefore the true drug targets and are used in Episphere™ screening and profiling assays.
- Assessment of selectivity across epigenetic target classes is key to understand the action of a drug and the risk of side effects.
Episphere™ works by:
- Capturing a sub-proteome of drug targets
The Episphere™ bead matrix captures more than 700 different proteins, including many epigenetic enzymes, in their native form. - Measuring the effect of compounds
A compound or drug added to a cell or tissue (either in vitro or in vivo) will compete with the Episphere™ bead matrix for binding of the enzyme targets and their complexes. Using mass spectrometry this competition is quantified and a full target profile is determined from a single tissue sample. - The same assay is also used to screen compound libraries with more than 100,000 compounds.