Targeting protein degradation uses different types of "degrading" drugs (degradants) to force a target protein (for example, a mutated protein that leads to disease development) into proximity to the cellular machinery that directs protein degradation. By inducing this proximity, target proteins are marked for destruction by the cellular proteasome.

This week, the Institute for Biomedical Research (IRB Barcelona) and the BBVA Foundation hosted the 39th Barcelona Biomedicine Conference, a meeting where leading minds could exchange ideas and discuss recent advances in the field of proximity-based pharmacology. The conference on "Proximity-Induced Pharmacology: Targeting Protein Degradation and Beyond" organized by Dr. Cristina Mayor-Ruiz from the Institute of Medical Research in Barcelona and Dr. Georg E. Winter from the CeMM Research Center for Molecular Medicine in Vienna (Austria) took place on May 22 and ended on May 24. Dr. Mayor-Ruiz and Dr. Winter are experts in the development of "degradants".

The event was attended by international experts from academia and industry such as Dr. Jay Bradner, renowned scientist in the field and founder of several start-ups, Dr. Craig M. Crews from Yale University and Dr. Alessio Ciuli from CeTPD, University of Dundee, both experts in PROTACs (a type of "degrader"), and Dr. Heidi Greulich from the Broad Institute of MIT and Harvard. The event also attracted representatives from the biotech and pharmaceutical industries.

"It is a great honor for me to organize this conference, with such an international presence. Through the exchange of ideas these days, we hope that new projects and collaborations will emerge that will push the field forward," said Dr. Mayor-Ruiz, head of the Laboratory for Targeted Protein Degradation and Drug Discovery at IRB Barcelona. Dr. Mayor-Ruiz spoke at a highly anticipated conference devoted to "molecular glue" drugs. These types of degradants are small molecules that facilitate interactions between proteins or other biomolecules, thereby facilitating their interactions, and exhibit very interesting properties due to their pharmacokinetic profile.

Targeted protein degradation is based on the intracellular protein degradation process. Aaron Ciechanover, Avram Hershko and Owen Ross, who won the Nobel Prize in Chemistry in 2004. The field has since opened up new ways to treat incurable diseases and to block proteins and processes thought to be untreatable with conventional medicines.

Pharmacology based on proximity induction is developing and now also considers the modification or degradation of other biomolecules, such as RNA molecules and bacterial proteins.

"What makes this conference unique is that, in addition to the high scientific level of the speakers, it is also focused on exploring the enormous potential of this technology. It is very exciting to work in such a new and evolving field," Co-organizer of the event and CeMM Austrian researcher Dr. Winter commented.

One day of the conference was dedicated to computational biology, which has played an important role in drug development and is now starting to find applications in pharmacology based on inducing proximity between biomolecules. Computer simulations and machine learning tools help select the most promising drug candidates. In addition, they can help optimize compounds by suggesting modifications that improve their properties.