Novel class of organic nitrate based nitric oxide donors
RTX has invented and is developing a platform of bifunctional redox-based small molecules formed from the covalent linkage of an organic nitrovasodilator domain that donates nitric oxide and a multifunctional redox catalytic domain. These agents remove toxic reactive oxygen species and deliver nitric oxide without the confounding effect of producing the potent toxin peroxynitrite via the diffusion-limited reaction of nitric oxide and superoxide. This bifunctionality confers unique pharmacologic properties verified in a series of in vivo disease models of inflammation, ischemia-reperfusion injury, acute lung injury, and pulmonary arterial hypertension. Candidate molecules have been developed for prevention of kidney reperfusion injury and thereby inhibition of acute renal failure, treatment of primary pulmonary hypertension of the newborn, and alleviation of peripheral arterial hypertension.
Novel prodrug inhibitors of poly(ADP-ribose) polymerase-1
RTX has invented and is developing a small molecule prodrug of a Phase 2 clinical-stage PARP-1 inhibitor. In experimental models of inflammation and reperfusion injury, this class of molecules diminishes neutrophil infiltration, preserves gross morphology and histologic structure, and protects tissue function. Additionally, the molecules overcome resistance to chemotherapy in tumors. A candidate molecule is in development for treatment via nebulization of Adult Respiratory Distress Syndrome and lung cancer.
Novel class of bifunctional potassium ATP-sensitive channel openers
RTX has invented and is developing is a platform of bifunctional redox-based small molecule prodrugs formed from the covalent linkage of a multifunctional redox catalyst with a mitochondrial-selective potassium ATP-sensitive channel activating moiety. Activation of the potassium ATP-sensitive channel is cytoprotective via its stimulation of the endogenous Ischemic Preconditioning pathway. Candidate molecules have been identified to treat: acute renal failure (via an intravenous route), primary graft failure after orthotopic lung transplantation (via aerosol), and primary open angle glaucoma (via a topical ophthalmic route).
Novel class of stable biological reductants
RTX has invented and is developing a platform of parenterally-administered pro-drugs that restore intracellular redox status by increasing intracellular bioreductive potential and activating the thioredoxin pathway. Candidate thioredoxin mimetic molecules are well-positioned to be of clinical benefit in the treatment of a wide range of redox stress-related clinical pulmonary and renal conditions, including acute renal failure, radiation-induced fibrosis, acute lung injury, and idiopathic pulmonary fibrosis.
Novel immunomodulator for treatment of inflammatory disease
RTX has invented and is developing a platform of variants of an endogenous signaling protein that restores regulatory T-cell balance by resetting the proportion of pathogenic Th1/Th17 cells and tolerance-inducing Tr1 cells. Subcutaneous administration of a candidate molecule profoundly suppresses tissue injury and organ dysfunction in experimental models of colitis, multiple sclerosis, sepsis, and pulmonary fibrosis.
