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Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
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Recent advances in proteasome inhibitor discovery
Yuri Pevzner1, Rainer Metcalf, Melanie Kantor
1University of South Florida, Chemistry, 4202 E Fowler Ave, Tampa, FL 33612, USA.
Expert Opinion on Drug Discovery
|April 4, 2013
Summary
Proteasome inhibitors show therapeutic potential for various diseases. This review explores diverse discovery approaches and scaffolds for developing effective proteasome inhibitors.
Area of Science:
- Biochemistry
- Pharmacology
- Drug Discovery
Background:
- Proteasome inhibition is a rapidly advancing research area with significant therapeutic potential.
- It offers a potent modality for treating numerous diseases and disorders.
Purpose of the Study:
- To review diverse approaches in proteasome inhibitor discovery.
- To highlight various scaffolds being investigated for this purpose.
Main Methods:
- Literature review of research from 2009-2012, with some earlier work.
- Analysis of experimental approaches, compounds, activities, and therapeutic potential.
- Exploration of discovery paths including library screening, drug repurposing, and novel scaffolds.
Main Results:
- Multiple strategies exist for proteasome inhibitor discovery.
- A wide array of chemical scaffolds are being explored.
- Compounds vary in their activities and therapeutic potential.
Conclusions:
- Successful proteasome inhibitor development requires a multifaceted strategy.
- Key considerations include screening, assays, mode of action, binding pocket selection, and delivery.
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