Chapter 7 - Cancer and Beyond: Discovery and Development of NO-Releasing Therapeutics

Abstract

Nitric oxide, the endogenous vasodilator, is a key signaling molecule that has been implicated in many biological processes and disease states. The manipulation of local nitric oxide concentration using drugs that deliver NO has been exploited for the treatment of many disease indications ranging from heart and circulatory disorders to the treatment and prevention of cancers. In this brief review, we focus on three drugs that have different mechanisms of NO release, eliciting distinct biological effects leading to contrasting potential applications: NBS-1120, an enhanced NSAID (eNSAID) based on the aspirin scaffold that releases nitric oxide and hydrogen sulfide; JS-K, an arylating NO donor; and RRx-001, an immune stimulatory agent that induces NO release indirectly. All three compounds affect the local concentrations of NO; however, their ultimate mechanisms of action are complex, arising from the multifaceted nature of nitric oxide and its context-specific activity. Here, we describe the known activity and safety of these NO donors, current hypotheses on their mechanism of actions, and their developmental status.