2015 Gordon Moore Medal – Dr. John A. McCauley


John McCauley_squareDr. John A. McCauley is a director of medicinal chemistry working in the field of HCV protease inhibitor drug design and synthesis at Merck Research Laboratories in West Point, Pa. HCV infection continues to represent a major health issue, with estimates of 130 million to 170 million people infected worldwide. Though hepatitis C is slow to progress, the disease ultimately leads to liver damage in up to 50% of affected individuals as well as carcinoma in a significant number of cases. Until 2011, standard treatment for HCV-infected patients was effective about 40% to 50% of the time. The success rate is improving dramatically with the introduction of new protease inhibitors.

Using a molecular modeling approach based on the enzyme crystal structure of HCV NS3 protease, Dr. McCauley and his team developed a strategy for macrocyclization of compounds to enhance interaction with the enzyme. To achieve these compounds, they designed a new synthetic route for constructing complex 20-membered macrocycles. His skills in design and synthesis led to multiple novel series of compounds with good pharmacokinetics and activity against resistant HCV mutant viruses. His efforts on these series were rewarded with the discovery of Vanihep® and grazoprevir, a next-generation compound currently in Phase III clinical studies.

Dr. McCauley earned a B.A. with honors in chemistry from Swarthmore College in 1991 and a Ph.D. in organic chemistry from the University of Pennsylvania, where he completed the total synthesis of rapamycin in the laboratory of Prof. Amos B. Smith, III. After working at Harvard University as an NIH postdoctoral fellow with Prof. Yoshito Kishi, he joined Merck in 1998 as a senior research chemist. He is currently a director of medicinal chemistry.

Over the past 17 years, Dr. McCauley and his group have been involved in the design and synthesis of nine compounds entering clinical development, including HCV NS3/4a protease inhibitors and additional compounds from antiviral and neuroscience programs. Dr. McCauley has co-authored 37 publications and is an inventor on 23 issued patents and 17 pending patent applications. In addition, he is a frequent guest lecturer who has given 18 invited presentations at national meetings and academic venues.