Molecular Determinants of Cell Permeability Beyond the Rule of 5

Authors: Matsson P, Lawless M
Software: ADMET Predictor®
Division: Simulations Plus

Molecules that violate conventional guidelines for druglikeness—such as the Rule-of-5—are of increasing interest as chemical probes and drugs for intractable pharmacological targets. Prominent examples of such unconventional molecules include cyclic peptides and non-peptidic macrocycles. However, a poor understanding of the molecular properties that govern their cell permeability, intracellular exposure and oral absorption has impeded their widespread use. In this webinar, I will discuss recent progress in the understanding of the molecular determinants of cell permeability for molecules in the chemical space beyond the Rule-of-5, with a particular focus on macrocycle permeability and the roles that environment-dependent molecular properties play in attaining desired pharmaceutical characteristics.

Pär Matsson is Associate Professor at the Department of Pharmacy, Uppsala University, Sweden and a principal investigator in the Drug Delivery Research Division. He is also Program Director for the Master’s Program in Pharmaceutical Modeling at Uppsala University’s Faculty of Pharmacy. His research is centered on the development of new computational and experimental methods to simulate, quantitate and visualize drug distribution at the tissue, cellular and subcellular scales, and on applying these methods to understand how the chemical features of drug molecules determine their cellular transport and subcellular targeting via membrane permeability and transporter interactions. His research interests also include how ligands outside the traditional small-molecule chemical space—in particular unusually large bioactive molecules—can be successfully developed into drugs.

Pär Matsson
Associate Professor
Department of Pharmacy, Uppsala University