Strategic Use of the Necessary Nitrogen Atom for Property-based Drug Design
Flash Talk with Lew Pennington, Ph.D.
Hosted by Drug Hunter's Director of Industry Research & Relations Dennis Koester, Ph.D.
December 5 2024 at 8 AM PDT / 11 AM EDT / 5 PM CEST
Small molecule drug design has evolved remarkably over the past several decades, and property-based drug design in particular has evolved considerably since its emergence over 25 years ago.
In this Flash Talk Lew Pennington will show how the “necessary nitrogen atom” can be leveraged for holistic property-based drug design, and will include an historical overview, key concepts, and several case studies.
Lew joined Drug Hunter as Scientific Director in 2024. Prior to that he served as Head of Platform Chemistry at Kymera Therapeutics. At Kymera, he co-invented the first molecular glue degrader in the portfolio. This degrader exploits a novel degron motif found in an undrugged transcription regulator, resulting in the launch of an immunology drug discovery program and an initiative to build a molecular glue degrader franchise.
Prior to Kymera Lew was a Research Fellow at Alkermes, where he initiated the orexin-2 receptor agonist program and served as the chemistry team leader, resulting in the invention of a clinical drug (ALKS 2680, Phase 2, Q2 2024) and an initiative to build an orexin-2 receptor agonist franchise.
Over the course of his 30-year career, Lew has contributed to the initiation of new drug discovery programs, the identification of validated hits, the invention of early and advanced leads, chemical probes, tool compounds, program go/no-go decision-enabling compounds, 2 clinical drugs, and 4 clinical candidates, 33 peer-reviewed publications, 18 granted US patents, and 34 WO patent applications.
In addition to drug discovery, Lew's research interests have included defining concepts, strategies, and tactics for multiparameter optimization in modern small molecule drug discovery: structure–brain exposure relationships, non-covalent sulfur interactions, the necessary nitrogen atom, positional analogue scanning (including nitrogen scanning), and holistic drug design. Notably, the necessary nitrogen atom and nitrogen scanning concepts helped inspire the creation of the area of synthetic chemistry known as skeletal editing.
Lew previously served a variety of roles as a synthetic and medicinal chemist at Amgen, Array BioPharma, and Eli Lilly & Co. He earned his B.Sc. in Chemistry (with Highest Honors in Chemistry) under the guidance of Professor Masato Koreeda at the University of Michigan, and a Ph.D. in Chemistry under the mentorship of Professor Larry Overman at the University of California, Irvine.