Design Principles in the Beyond Rule of 5 Space

Описание: Modern drug discovery is now capable of targeting previously considered undruggable targets. The complexity of medicines is increasing, with many drug molecules and modalities violating at least one of Lipinski's Rule of 5 (Ro5) parameters. In the "beyond Rule of 5" (bRo5) space, unique design principles are essential. Optimizing permeability and lipophilicity is particularly challenging due to their typical anti-correlation.

In this Flash Talk, Henrik Moebitz discussed design principles in the bRo5 space. As a computational chemist, he is an expert in navigating bRo5 chemical space using physics-based computation. Henrik explained how an analysis revealed that 3D PSA and logP thresholds of oral Ro5 and bRo5 candidates coincide. He introduced neutral TPSA as a new parameter for lead optimization in bRo5 drug campaigns and demonstrated its optimization across four first-in-class campaigns, which led to clinical candidates or approved drugs. Notably, Henrik led the medicinal chemistry team that discovered the first-in-class WRN inhibitor, HRO761.

00:00 Introduction
02:25 Ice-breaker questions
10:49 Drug Hunter case study preview
13:00 Presentation
50:34 Q&A

Presented by Henrik Moebitz, Ph.D. Director- CADD, Global Discovery Chemistry with host Dennis Koester, Director of Industry Research and Relations Drug Hunter

Henrik trained as an organic chemist and completed his Ph.D. in biochemistry at the University of Freiburg. He furthered his studies in enzyme catalysis through postdoctoral training at UC Santa Barbara, focusing on the molecular mechanics of enzymes. In 2005, he joined the department for computer-aided drug discovery (CADD) at Novartis in Basel. Currently, he co-leads the Basel CADD group and oversees several medicinal chemistry projects. Henrik is the author of over 50 publications and patents, with a significant body of his recent work still awaiting publication.

Presented on July 11, 2024, as part of our Drug Hunter Flash Talk series.

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