The United States Bullion Depository in the state of Kentucky, popularly known as “Fort Knox,” is a symbol the world over of impregnable security and protection.
Another vault-like structure is the dinitroazetidine ring that led EpicentRx small molecule, RRx-001 (nibrozetone), contains, circled in red below.
We also refer to RRx-001 somewhat tongue-in-cheek as “Fort NOx” because unlike the permanently locked-down Fort Knox, the dinitro azetidine ring of RRx-001 unlocks itself in the vicinity of diseased tissues, releasing therapeutic ‘nitrogen oxides’ or NOx such as nitric oxide (NO), and N2O (nitrous oxide) as well as nitric acid, nitrous acid (HONO), and several others. Nitric oxide, for one, acts as a vasodilator that boosts blood flow to diseased tissues, which, almost without exception, being chronically under perfused and poorly oxygenated, benefit from the increased circulation.
Also, unlike Fort Knox, the RRx-001 Fort NOx traffics not in gold but in platinum. In two ongoing clinical trials, the Phase 3 REPLATINUM and the Phase 2b KEVLARx, RRx-001 is combined with the platinum chemotherapy agents, carboplatin and cisplatin, to hopefully make them not only more active in diseased tissues, which is what the data strongly suggest, but also, very importantly, less toxic in non-diseased ones.
It took years and years of painstaking research for us to work out this dichotomous mechanism of action, which governs not only what RRx-001 does but how, where and when.
We often refer to these formative, research-intensive years as the School of Hard NOx.