The Proteolysis Targeting Chimera (PROTAC) technology can be used to control protein levels in cells. This technology uses small molecules (PROTACs) that recruit target proteins for ubiquitination and subsequent proteasomal degradation. A PROTAC is a bifunctional molecule consisting of an E3 ligase binding ligand and a protein target ligand connected by a linker. Traditional pharmacological approaches are based on protein inhibition and therefore dependent on an occupancy based mode of action. In comparison, the PROTAC technology uses a catalytic mode of action that irreversibly inhibits protein functions as a result of protein degradation. The PROTAC technology can overcome limitations associated with the inhibition-based approach such as off-target side effect resulting from the need of high in vivo/systemic concentration to maintain protein inhibition and most importantly the need of an active site, thus limiting the drug target space. We will present our present efforts to expand the PROTAC technology to the currently undruggable target space.

PROTACs – Small molecule induced protein degradation

255th National Meeting (2018)

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