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Chemoproteomic trailblazer advances covalent candidate into the clinic, pushes allosteric agenda
Vividion CEO Aleksandra Rizo discusses emerging lessons from the firm’s use of fragment-based screening — including the potential for allosteric covalent drugs to drive different functional effects through a single binding site.
Although small molecules can be excellent at finding and binding deep pockets on proteins of interest, many therapeutic targets with smooth surfaces remain hard to get a good handle on. Partly as a consequence of the resulting lack of leads, less than 10% of human proteins are currently drugged. So when chemical biologist Benjamin Cravatt and colleagues at Scripps reported in Nature in 2016 that covalent fragments could be used in a target-agnostic manner to bind irreversibly to targets with shallow pockets, the medicinal chemistry community took note.