New drug development article // Drug Repurposing

New drug development article

Antiviral drug discovery and developmentJoseph Vacca, Ph.D. Executive Director, Medicinal Chemistry West Point, Merck, Pennsylvania, USA

In the mid-1990s, a new class of antiviral drugs known as HIV protease inhibitors revolutionized the treatment of HIV infection. Being involved in this transformation has been the best career experience for Joseph Vacca, Executive Director of the Department of Medicinal Chemistry at Merck, who was the project leader and one of the co-inventors of the first-generation HIV protease inhibitor indinavir. "It was thrilling to see how HIV went from being a death sentence to being a chronic, manageable disease for many people, " recalls Vacca. "Many better treatments now exist, but I feel that indinavir helped to show people what a potent drug could do, and also taught people how to make better ones."

Vacca's scientific career began with Peter Lansbury Sr at The State University of New York at Buffalo, USA. "I chose organic chemistry because I enjoyed the challenge of lab work and the gratification of planning a synthetic sequence that resulted in a product, " he says. When he was searching for a position during the last year of his graduate studies, he sent his résumé to an old lab colleague who was working at Merck, and was offered a position at the West Point site. "Medicinal chemistry appealed to me because of my interest in biology and the chance of being able to discover a drug. At Merck I could continue to do high level synthetic chemistry and was encouraged to publish in the scientific literature, " he explains.

For 12 years, he worked in the laboratory as a synthetic chemist on projects ranging from 2 adrenoceptor antagonists for depression, the synthesis of myo-inositol polyphosphates to study cell signalling pathways and finally to HIV protease inhibitors before moving to a managerial role. "My attraction to managing a group was to be involved with several drug discovery projects and to be able to interact with many high level scientists within our department and across the organization, " says Vacca. Now, he oversees many of the Department's drug discovery projects and acts as mentor and consultant to the chemistry heads who report to him. It is this interaction with talented colleagues that he most enjoys. "It is a pleasure to come in every day and see what kinds of new discoveries have been made, " Vacca says.

Of course, given the high attrition rates in drug discovery and the 26 years he has been at Merck, Vacca is familiar with the ongoing challenges in the field. "I have personally failed at every point in the path to a drug and it is usually from something unexpected." Still, successfully tackling these challenges is very rewarding. "I am excited to see clinical data from our compounds and to see what effect they have on the lives of patients, " says Vacca. "I was lucky enough to be the chemistry director when we started our recent integrase project [which has now resulted in the approval of the first HIV integrase inhibitor, raltegravir] and can see once again how a compound with a new mechanism of action affects the lives of people."

David M. Burger, Pharm.D., Ph.D. Associate Professor, Department of Clinical Pharmacy and Nijmegen University Centre for Infectious diseases (NUCI), Radboud University Nijmegen Medical Centre, The Netherlands

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