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Inhibition of E3 ubiquitin ligases, which provide substrate specificity to the ubiquitin proteasome system, is an attractive strategy to inhibit the degradation of a small subset of proteins. Skaaret al. discuss the progress that has been made in the development of therapeutic inhibitors of E3 ligases, in particular the SKP1–CUL1–F box protein (SCF) ubiquitin ligase complexes, and the challenges that lie ahead.
The failure of many clinical trials of the pioneering matrix metalloproteinase (MMP) inhibitors in oncology owing to lack of efficacy and side effects, such as musculoskeletal toxicity, reduced enthusiasm for further development of the drug class. Vandenbroucke and Libert discuss how greater knowledge of MMP biology, as well as the development of more specific MMP inhibitors, could provide new opportunities to use such agents in the treatment of sepsis and other inflammatory disorders.
The Critical Path Institute brings scientists from regulatory agencies, industry and academia together to improve drug development and regulatory processes.