Tuesday, 20 June, 2023 08:30 - 10:30
SC: Protein Degraders: A Focus on PROTACs from a DMPK Perspective
This course focuses on proteolysis targeting chimeras (PROTACs) and will cover topics relevant to developing them as oral therapeutics. As an introduction, we will examine what they can accomplish that small molecules cannot, importance of ternary complex formation, and how proteomics is essential for their development. PROTACs lie in Bro5 space, and we will cover the significance of this for developing them as oral drugs, such as how their physicochemical properties influence solubility and permeability. We will also go into the important topic of metabolism of PROTACs and consider some unique safety issues of PROTACs.
Topics to be Covered:
- Benefits of PROTACs compared to small molecules
- Challenges of developing PROTACs in the context of Bro5
- Importance of intramolecular hydrogen bonds for solubility and permeability
- Determining chameleonicity and its importance for PROTACs
- Metabolism and influence of linker length on stability
- Safety issues unique to PROTACs
Who Should Attend:
Scientists in the field of proteolysis targeting chimeras (PROTACs) who would like to deepen their understanding of these molecules and the physicochemical attributes that may contribute to their success as oral drugs. ADME scientists and medicinal chemists wishing to understand PROTACs from a drug safety and metabolism perspective. Graduate students and academic scientists interested in learning more about this rapidly developing new drug modality.
John Erve, PhD, Senior Principal Scientist, Jerve Scientific Consulting
John Erve is from Chicago and studied Chemistry (BS, MS) at the University of Chicago and earned a PhD in Toxicology at Oregon State University. Following postdoctoral work at Vanderbilt (1995-1999) he joined BD-Biosciences (Woburn, MA) as a Study Director. In 2002, he joined AstraZeneca (Sweden) where he characterized reactive metabolites. In 2004 he joined Wyeth (Collegeville, PA) as a Principal Scientist responsible for metabolite identification. In 2010, John joined Novartis (Cambridge, MA) as a Lab Head in Analytical Sciences. John returned to drug metabolism at Elan Pharmaceuticals (San Francisco, CA) in 2012 and later formed Jerve Scientific Consulting, Inc to help small biotech companies in the Bay area with their drug discovery efforts. John was a certified D.A.B.T. from 2004 to 2019.