Enhancing Targeted Protein Degradation by Structure-Based PROTAC Design (IL01)
by Dr Siying ZHONG (University of Dundee, Dundee, UK)
Targeted protein degradation using proteolysis targeting chimeras (PROTACs) has emerged as a powerful modality in chemical biology and drug discovery. PROTACs hijack the cellular ubiquitin–proteasome system and mediate the degradation of the POI by forming a ternary complex with the POI and an E3 ubiquitin ligase. Research in our group has shown that the increased stability of the PROTAC-induced ternary complex enhances the selectivity and efficiency of degradation. In this presentation, I will showcase two examples to demonstrate the rational structure-based optimisation of PROTACs guided by structural and biophysical studies of ternary complex formation.
Targeting Non-Coding RNAs Using Synthetic Small Molecules: Scope and Applications (IL02)
by Dr Maria DUCA (University of Côte d'Azur, Nice, FR)
Targeting non-coding RNAs using synthetic small molecules is a major challenge for current medicinal chemistry. Some examples of the design and synthesis of selective RNA ligands targeting oncogenic microRNAs will be reported together with their potential applications.
Peptiligase Enzymes (IL03)
by Dr Leendert VAN DEN BOS (EnzyTag, Nuth, NL)
A brief introduction into the increasing complexity of new chemical entities reaching the market will be given. The latest examples of these include amongst other macrocyclization, ADCs and LYTACs. Older but still very much relevant are Insulin and its derivatives. These complex compounds require innovative technologies from discovery all the way to commercial. This talk focuses on the potential of the peptiligase technology platform for these drug classes.
Activation of the Hippo Pathway via Targeting of Transcription Factor TEAD Using Designed Tertiary Protein Structure Mimetics (IL04)
by Dr Hélène ADIHOU (AstraZeneca, Dortmund, DE)
The Hippo pathway, under the modulation of the TEAD transcription factor, plays a crucial role in the regulation of organ size, tissue homeostasis, and regeneration. TEAD transcriptional activity is controlled through the formation of a protein-protein interaction network with the YAP/TAZ co-activators or VGL4 co-repressor. To inhibit the formation of the repressor complex, we designed a tertiary protein structure mimetic of VGL4. Our proteomimetics induce cell proliferation via the promotion of YAP/TAZ interaction with TEAD, paving the way for novel regenerative therapies.
Click-Cleavable Antibody-Drug Conjugates (IL05)
by Dr Marc ROBILLARD (Tagworks Pharmaceuticals, Eindhoven, NL)
Robillard will present Tagworks click cleavable ADC approach that uses a bioorthogonal bond cleavage reaction for selective antibody-drug cleavage in vivo instead of relying on intracellular biological activation mechanisms.
Targeting the Tumor Microenvironment for Therapeutic and Diagnostic Purposes (IL06)
by Prof. Sebastien PAPOT (University of Poitiers, Poitiers, FR)
Description to be received.