The Power of Chemistry in Public Health: Drug Design from the Lab Bench to the Consumer

Organizers: Emilly Obuya and Robert Congdon, Department of Chemistry, Binghamton University, P.O. Box 6000, Binghamton, NY 13902, Email: gsspc.binghamton@gmail.com

In the morning session, Megan Fegley, GSSPC Vice chair, provided the welcome address.  Throughout the morning and afternoon sessions Robert Congdon, GSSPC program chair, acted at the presider of the symposium.  Magid Abou-Gharbia, School of Pharmacy, Temple University, presented Strategies for the discovery of innovative therapeutics.  This presentation focused on the challenges pharmaceutical companies face such as reduced efficiencies, declining innovation and the industry’s tarnished image. Academic drug discovery centers were discussed as an initiative to address these challenges by facilitating the transition of academic ideas and breakthroughs into drug discovery opportunities, a current innovation gap. Peter Bernstein, PhaRmaB LLC, presented The evolving role of chemistry in small molecule drug discovery.  The role of the medicinal chemist has transformed from a synthetic organic chemist developing small molecule drugs to a conductor/composer who integrates input from synthetic, ana­lytical, computational, structural biological, physical and informatics chemists.  The presentation discussed how the functions that chemists fill in R&D efforts have become more diverse, com­plex and specialized, but at the end of the day an effective and safe small molecule drug is still key.  Patrick Lam, Lam Drug Discovery Consulting, LLC, presented Structure-based discovery of a novel factor Xa inhibitor, Eliquis®/Apixaban, as a new anticoagulant and the discovery of Chan-Lam coupling reaction.  Factor Xa is at the junction of the intrinsic and extrinsic pathways of Thrombosis and preclinical data demonstrated that blocking FXa is an effec­tive approach for anticoagulation. Using structure-based drug design tools, Bristol-Myers Squibb has discovered a novel class of potent, se­lective and orally bioavailable Factor Xa inhibitors culminating in Eliquis®/Apixaban, with Eliquis® in Phase III clinical trials. During the optimization process, the powerful Chan-Lam Coupling reaction was discovered, a copper promoted C-X bond cross-coupling via boronic acids which is a complementary reaction to the Suzuki- Miyaura Coupling.

Steven Tannenbaum, Massachusetts Institute of Technology, presented The chemistry of inflammation and cancer: Lessons from inflammatory bowel disease.  This presentation focused on the discovery and application of serum biomarkers of inflammatory bowel disease (IBD) to monitor disease severity and activity in IBD patients. Using a mouse model of IBD and colon cancer, it was shown that bacterial infection leads to chronic inflamma­tion, dysplasia and cancer, by a process that is promoted by pro-inflammatory cy­tokines/chemokines, oxidative and nitrosative stress and DNA/protein damage. The invading inflammatory cells produce a mixture of chemicals, including NO, H2O2, HO•, CO3−•, HOCl, and NO2•, which damage and lead to degradation of proteins, lipids and nucleic acids, inducing mutation and/or cell death.  Bonnie Charpentier, Metabolex Inc, presented Chemistry and regulatory in drug development.  Shifting the focus to the regulatory requirements for development and approval, this presentation highlighted the history and changes in regulation and guidelines, often as a result of public safety disasters. Since chemistry is involved in drug design, synthesis, isolation, formulation, manufacturing, quality testing and measurement, training in chemistry can be helpful in guiding drug de­velopment, not only in the laboratory but in such careers as regulatory affairs. Therefore, the current role of chemistry in the development and approval of new drugs was also discussed.

In the afternoon session, Bob Maughon, Dow Wolf Cellulosics, presented Health by design: Dow Wolff Cellulosics excipient innovations for the pharmaceutical industry.  This presentation discussed how Dow Wolff Cellulosics tailors polymer chemistry, mor­phology and blending into solutions that enable customers to provide consum­ers healthier outcomes. In modified release, research enables formulators and manufacturing teams to address regulatory and sustainability initiatives, focusing on modeling the performance design space to better predict structure-property relationships; enabling enhanced quality-by-design; the development of materials that can deliver direct compression; and improved technologies for osmotic delivery systems. In immediate release, developments in low viscosity HPMC polymers and their applications to improve product performance and sus­tainability vs. conventional methods in coatings, capsules and granulation was primarily discussed. Michael Hurrey, Vertex Pharmaceuticals Incorporated, presented Development of blockbuster drugs in the 21st Century: A personal journey.  From the perspective of the speaker, the talk went through the key factors needed to develop a drug through clinical trials and eventually to launch it. Examples of the blood, sweat, tears, and luck it took him to succeed in launching two drug candidates was also discussed.

Nancy Lewen, Bristol-Myers Squibb, presented Forensics in the pharmaceutical industry.  Unfortunately, counterfeit pharmaceuticals are becoming more prevalent in domestic and foreign marketplaces. With patient safety at the forefront, the pharmaceutical indus­try is working to prevent and detect the manufacture and distribution of counterfeit pharmaceuticals. Therefore the talk highlighted work being performed in the pharmaceutical industry to identify counterfeit products as well as their source.  Elizabeth Cormier, FDA Center for Veterinary Medicine, presented Chemists, chemistry, and the FDA: Building quality into drug Manufacturing.  This presentation explored the importance of quality controls and the role FDA plays in drug development.  Throughout the last century, members of the FDA staff, many of them chemists, have been striving to protect and promote public health. A component of any drug application is the Chemistry, Manufacturing, and Controls (CMC) technical section which is designed to ensure that the drugs our children take tomorrow are as safe and ef­fective as the ones we approve today.   At the conclusion of the afternoon session, Paul Tanui, GSSPC logistics chair, provided the concluding remarks.