What is the role of physico-chemistry in DMPK?

Recorded: September 2021

This webinar will define and explore physicochemical properties and their influence on DMPK parameters such as clearance, volume of distribution and oral absorption.  The key properties and how they are best measured in contemporary practice will be presented.  In addition, case studies will illustrate how physicochemical properties can be manipulated by skilled medicinal chemists to improve the DMPK outcomes with experimental molecules during optimisation.

Agenda

1. How physicochemical properties defines DMPK properties?
   • General overview of physico-chemistry properties and how they influence absorption, distribution, clearance, etc.
2. How do we measure physicochemical properties?
   • How we measure lipophilicity (log D, log P, chrom log P etc), ionization (pKa), solubility (kinetic and thermodynamic). This will cover the theoretical and practical aspects of the methods.
3. How do we use physicochemical properties to mitigate DMPK issues in design?
   • General principals of using physicochemical properties to mitigate DMPK issues in design using a series of case studies

Moderated by 

Barry Jones, Ph.D. - Senior Research Fellow, Metabolism at Pharmaron

Speakers

Robert Young, Ph.D. - Medicinal Chemistry Consultant at Blue Burgundy

Following BA/DPhil degrees at University of Oxford and a Post Doc at Ben May Institute, University of Chicago, Rob joined Wellcome in 1990. After navigating many changes in his career, he soon became a Scientific Leader and was elected as a Fellow at GSK. Rob made significant contributions to six development candidates in antivirals before moving to early stage discovery (2006) where he fulfilled leadership roles in numerous H2L programs. He was then appointed to numerous GSK cross-disciplinary initiatives and communities including in silico predictive modelling, DMPK, Physical Chemistry, Stability and Safety. Today, Rob is the author/inventor of 100 publications/patent applications, an honorary visiting Professor at University of St Andrews, and after taking an early retirement from GSK in 2019, Rob is principal at Blue Burgundy, a consulting firm he created to provide innovative thinking in drug discovery.

Chunyan Han, Ph.D. - Senior Director, in vitro ADME, DMPK at Pharmaron

Dr. Han is Senior Director in the DMPK department of Pharmaron with 12-years of hands-on and managerial experience in drug discovery and development. Since she joined Pharmaron in 2009, she has made significant contributions in setting up the in vitro ADME platforms especially for all the cell-based assays. Her responsibility now includes project coordination, new assay development and validation, and acting as DMPK lead in integrated drug discovery projects for data interpretation and molecular design. Dr. Han has excellent knowledge of in vitro and in vivo ADMET/PK technologies and mass spec instruments. Her experience covers early stage drug discovery to late stage regulatory DMPK studies for small molecules. In Pharmaron, Dr. Han leads a team in building up cell-based assays, including permeability screening, drug transporter, cell-based metabolism and CYP induction, etc.

Sébastien Degorce, Ph.D. - Associate Director of Medicinal Chemistry at Pharmaron

Dr. Degorce joined Pharmaron in November 2020. Prior to this, he spent 13 years at AstraZeneca (France, U.K. and U.S.A.) where he was a drug designer within the Oncology Innovative Medicines Unit. Sébastien contributed to the progression of multiple projects in the fields of kinases, nuclear hormone receptors, epigenetic targets and immuno-oncology. He particularly enjoys sharing his passion for medicinal chemistry and its applications to drug discovery. He completed an industrial post-doc with Sanofi-Aventis before joining AstraZeneca. He is the co-author/co-inventor of over 35 peer reviewed publications, patent applications and oral presentations at scientific meetings.