Discovery and Clinical Evaluation of MK‐8150 A Novel Nitric Oxide Donor With a Unique Mechanism of Nitric Oxide Release

摘要

BackgroundNitric oxide donors are widely used to treat cardiovascular disease, but their major limitation is the development of tolerance, a multifactorial process to which the in vivo release of nitric oxide is thought to contribute. Here we describe the preclinical and clinical results of a translational drug development effort to create a next‐generation nitric oxide donor with improved pharmacokinetic properties and a unique mechanism of nitric oxide release through CYP3A4 metabolism that was designed to circumvent the development of tolerance.