A novel prodrug for K+-ATP channel activation in the glaucomatous eye

DESCRIPTION (provided by applicant): Radikal Therapeutics (RTX) is developing a revolutionary bifunctional small molecule (R-801) for topical therapy of primary open angle glaucoma (POAG). R-801 is constructed from the covalent fusion of 2 chemical domains, each with demonstrated tissue protective properties: 1) a mito-K+-ATP channel activating moiety derived from the isoform non-selective K+-ATP channel opener pinacidil, and 2) a pyrrolidine nitroxide spin trap domain (hydroxymethylproxyl, HMP ) that actsas superoxide dismutase (SOD) and catalase mimetics and a peroxynitrite decomposition catalyst. By design, R-801 targets 2 independent mechanisms of injury each considered critical to the pathogenesis of POAG: 1) intraocular hypertension (IOH), and 2) neuronal redox- mediated cell death. Our preliminary data reveal that R-801 reduces intraocular pressure (IOP) in explanted human eyes and in topically-treated mice. The present application is intended to extend these initial observations by elucidating: