Three major targets for pharmacologic intervention have been developed based on the Company's original research in the regulation of cellular responses to conditions leading to tissue injury, such as hypoxia (low oxygen), ischemia-reperfusion, hyperglycemic metabolism (diabetes), elevated intraocular pressure or angiogenic dysregulation. These pathologic conditions alter cellular metabolism and energetics, activate inflammatory pathways, and result in cell death through necrosis or apoptosis. Inotek's pharmacological targets include:

1. Adenosine Agonism. Adenosine, an important extracellular signaling molecule, participates in a wide variety of physiological and pathological processes. Under metabolically stressful conditions, such as those that occur during injury, ischemia, and inflammation, this purine nucleoside's extracellular concentration increases dramatically. This protective response to injury, or the activation of associated signaling pathways, can be achieved by metabolically stable analogs of adenosine acting through specific adenosine receptor subtypes. There are four subtypes of adenosine receptors (A1, A2a, A2b, A3), each with unique physiological effects, making selectivity a critical aspect of adenosine therapeutics.
2. PARP Inhibition. Poly (ADP-ribose) polymerases (PARPs) are a family of nuclear enzymes implicated in the regulation of multiple physiological cellular functions, including DNA repair, gene transcription, protein modification and cell signaling. Over-activation of PARP results in pathologic alteration of cellular metabolism, activation of inflammatory pathways, perturbation of cellular energetics, and cell death through necrosis or apoptosis.
3. Peroxynitrite Decomposition and Superoxide Dismutase (SOD). Reactive oxygen species (ROS) such as superoxide exhibit a wide array of tissue-damaging cytotoxic effects, reacting with and attacking a variety of biomolecules (including proteins, lipids, and DNA) important for normal tissue metabolism and growth. Lower concentrations of oxidants usually trigger apoptotic death, whereas higher concentrations induce necrosis, with cellular energetics (ATP and NAD) serving as a switch between the two modes of cell death. Peroxynitrite scavengers and superoxide dismutase mimetics limit tissue damage induced by these oxidants.