SC5: MACROCYCLIC COMPOUNDS FOR DRUG DISCOVERY: OPPORTUNITIES, CHALLENGES, AND STRATEGIES

MONDAY, AUGUST 24 | 2:00 - 5:00 PM

Macrocyclic compounds occupy an important underexplored chemical space between small molecules and biologics. However, these structures possess critical characteristics typically attributed to only one of these two broad categories, which makes them particularly attractive for modulating traditionally difficult target classes such as protein-protein interactions. Beginning last decade, the advent of and improvements in the technologies for accessing these molecules and libraries thereof have led to significant progress being realized with this interesting chemical class and the number of synthetic macrocycles entering into clinical trials has steadily increased. This course will discuss important past and recent advances in the field, including an improved understanding of the properties of macrocyclic molecules, in particular as they relate to their PK-ADME profiles, and specific case studies of these compounds in drug discovery and development. The course is suitable for all those who wish to learn more about the current state and future potential of this evolving area regardless of their level of knowledge.

Topics to be Covered:

• Unique characteristics of macrocycles
• Factors affecting cell permeability and PK/ADME properties
• Synthetic strategies for macrocyclic compound libraries and macrocyclization challenges
• Drug discovery and development examples
• Additional medicinal chemistry applications of macrocyclic molecules
• Perspectives on remaining challenges and future opportunities for macrocyclic molecules

Instructors:

Eric Marsault, PhD, Professor, Medicinal Chemistry and Pharmacology, University of Sherbrooke

Éric Marsault studied chemistry at École Supérieure de Chimie Organique et Minérale (ESCOM) in Paris and at Université Pierre et Marie Curie (Paris VI), then obtained a PhD in organic chemistry from McGill university under the direction of the late Pr George Just in 1996, where he worked on an asymmetric synthesis of DNA phosphorothioates. Following an 18-month period as a visiting scientist with Sanofi (Milan), he joined the lab of Pierre Deslongchamps in Sherbrooke for postdoc (1998-2000), working on the transannular iels-Alder strategy for synthesis of diterpene-like products. He then joined the recently incorporated Néokimia (which became Tranzyme Pharma in 2004) as a scientist (2000), then group leader (2001-2006) then director of medicinal chemistry (2006-8). During these years of construction and intense development of the company, he had the opportunity to develop his skills in combinatorial chemistry, medicinal chemistry and drug discovery, assuming responsibilities in platform development, medicinal chemistry, lead optimization and manufacturing which led to the discovery of several preclinical macrocyclic candidates on G protein-coupled receptor targets, two of which reached clinical phases 2 and 3 for gastro-intestinal disorders.

In 2009, he joined Université de Sherbrooke (Dpt of Pharmacology) as associate professor and opened a medicinal chemistry lab at the Institut de Pharmacologie de Sherbrooke (IPS). His lab, which now includes 18 students, focuses on the use of small molecules to validate emerging biological targets, and functions in a highly collaborative way in which there is always a partner from pharmacology, physiology, biology or medicine. This exposes students to an interdisciplinary environment and gives them access to complementary expertise in terms of mentoring. His works have lead to several collaborations with pharmas, including the first investment of the recently founded Néomed on the development of host-based inhibitors against influenza. He is co-author of over 30 research papers and co-inventor of over 35 patent applications. Since 2013, he is director of the FRQS-funded Réseau Québécois de Recherche sur le Médicament (www.rqrm.ca) and director of the Institut de Pharmacologie de Sherbrooke www.usherbrooke.ca/ips).

Mark Peterson, PhD, COO, Cyclenium Pharma, Inc.

Dr. Peterson recently co-founded Cyclenium Pharma with a focus on developing and utilizing a next generation macrocyclic technology for novel drug discovery. Prior to Cyclenium, Dr. Peterson was Vice President, IP & Operations at Tranzyme Pharma, a pioneer in the use of small molecule macrocycles in pharmaceutical research, where he led the chemistry R & D efforts during the technology development stage of the company and the initiation of its discovery programs, then later was instrumental in contributing to the development of its clinical portfolio and building an extensive portfolio of over 120 patents and applications. Previously with Monsanto and Advanced ChemTech, he has worked in a variety of research areas including structure-based design, solid phase organic chemistry, combinatorial technologies, synthetic automation, heterocycles, unnatural amino acids, peptides and peptidomimetics. A native of Wisconsin, he received his PhD in Organic Chemistry from Washington State University and conducted post-doctoral research at the University of Minnesota, the last year receiving an NIH National Research Service Award. He is author or co-author of over 85 publications and abstracted presentations plus three book chapters, as well as co-inventor on over 25 patents.

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