Abstract
Target(ed) protein degradation (TPD) is a novel paradigm in drug discovery and a promising therapeutic strategy. TPD is based on small-molecules that catalyze the degradation of proteins by re-directing the ubiquitination activity of ubiquitin E3 ligases. Its unique molecular pharmacology enables robust, selective and fast elimination of proteins in cellular assays and in vivo. In addition to possible clinical applications, TPD is also emerging as an attractive alternative to traditional pharmacologic or genetic perturbation strategies. Directly acting degraders, as well as chemical-genetics derivatives offer unique opportunities in the pre-clinical identification, characterization and mechanistic validation of therapeutic targets.
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