Application of nitric oxide in drug discovery and development.

INTRODUCTION: It is becoming increasingly clear that many diseases are characterized or associated with perturbations in nitric oxide (NO) production/signaling. Therapeutics or strategies designed to restore normal NO homeostasis will likely have broad application and utility in human health. This highly complex and multi-step pathway for NO production and subsequent target activation provides many steps in the endogenous pathway that may be useful targets for drug development. Important therapeutic areas for NO-based therapies are inflammatory disorders, cardiovascular diseases, erectile dysfunction and metabolic disorders. AREAS COVERED: The following review will discuss the endogenous NO pathway, highlight the current market and indications for NO-based therapeutics, as well as identify pathway targets currently under drug development. Each step along the NO pathway will be discussed including exogenous sources of NO, use of precursors to promote NO production and downstream pathways affected by NO production with advantages and disadvantages highlighted for each. EXPERT OPINION: Development of NO-based therapeutics is and will continue to be a major focus of biotech and pharmaceutical companies. Understanding and utilizing dietary and nutritional strategies to restore NO homeostasis could allow for safer, quicker marketing of products that may be just as efficacious as drugs designed against specific targets.