Shattuck Lecture: Nitric oxide and cyclic GMP in cell signaling and drug development

Our understanding of the nitric oxide and cyclic GMP signaling pathways has advanced considerably in the past three decades. Although there has been substantial progress in this area, numerous questions remain unanswered. Nevertheless, these pathways have provided us with numerous novel targets through which many approaches to a vast array of disorders will be discovered and developed. These advances will continue to require the collaborations of biochemists, molecular biologists, cell biologists, physiologists, pharmacologists, medicinal chemists, and clinical scientists. As a clinical pharmacologist, drug discoverer, and drug developer, I believe it is possible to develop highly selective and specific new therapies without unwanted side effects. The more we know about the biochemical regulation of various macromolecular players and isoforms of all of the participants in the signaling cascade, the more likely we will be to succeed. Various formulations, selective delivery systems, and the pharmacokinetic properties of the agents can also assist the process. I expect to see many new agents coming from the field of nitric oxide-cyclic GMP research over the next one to two decades that will effectively contribute to our therapeutic armamentarium. Copyright © 2006 Massachusetts Medical Society.