Targeted Protein

Degradation: Eliminating

the “undruggable target”

Webinar Summary:

Targeted Protein Degradation (TPD) has emerged as a new therapeutic strategy for targeting disease-causing proteins by modulating their intracellular abundance. In theory, the mode-of-action of degraders is expected to also render those proteins druggable, which, either lack functional activity or have been resistant thus far towards direct inhibition by small molecules. TPD is based on the induced proximity of the target and proteins involved in the cellular clearance pathways, i.e. components of E3 ubiquitin ligases. Protein degraders come in two different flavors: bivalent proteolysis-targeting chimeras (PROTACs) and monovalent, structurally simpler molecular glue (MG) degraders. Starting with the first reported PROTAC a little more than two decades ago, the field has been constantly growing. Today, the first candidates are in late clinical development and degraders indeed might contribute to a new “era of biopharmaceutical innovation” carried by multispecific drugs (Nature 580 (2020), 329-338).

In this webinar, we will focus on cell-based assays that allow target protein levels to be monitored and enable the identification of small molecule degraders via high-throughput screening of suitable compound collections. We will discuss complementary cell-based and cell-free assays to support the characterization and further development of hit compounds. Finally, we will introduce a new platform designed and operated in collaboration with our partner Symeres to facilitate PROTAC discovery.


PROTAC, molecular glues, degraders, degradation, E3 ubiquitin ligase, protein-protein interaction, ternary complex, target engagement, UPS, proteasome, automated WB, cell-based assay, biochemical assay


  • Lucia Iuzzolino, Principal scientist, Biochemistry group, Axxam

  • Elisa Onesto, Principal scientist, Cell biology, Axxam

Lucia Iuzzolino is currently Principal Scientist in the Biochemistry group at Axxam with extensive experience in the field of HTS assay configuration on therapeutically relevant targets. She is responsible for the strategic design and development of functional biochemical assays for HTS across a broad range of targets including different enzyme classes, hetero-multimeric protein complexes, protein-peptide and protein-protein interactions. She has a PhD in Enzymology from the Philipps-Universität Marburg (Germany). She joined Axxam in 2004 after many years of research experience on function and structure of multimeric protein complexes with different biochemical and biophysical approaches. During her career, she was co-author of several peer-reviewed publications in highly ranked international journals.

Elisa Onesto is currently working as a Principal Scientist in the Cell Biology group at Axxam. She holds a Master’s Degree in Pharmaceutical Biotechnologies and a PhD in Endocrinology and Metabolic Science, from the University of Milan.  During these years she worked in the Neuroscience field studying mechanisms potentially causing ALS. The focus of her research was protein aggregation and pathways for cellular clearance (such as UPS and autophagy) as well as RNA metabolism. She is both author and co-author of peer-reviewed scientific publications. At Axxam she has developed and set-up many cell-based assays for HTS, using different and up-to-date technologies. 

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