Patents related to therapeutic activation of K(ATP) and K(2P) potassium channels for neuroprotection: ischemic/hypoxic/anoxic injury and general anesthetics.
Keywords
Abstract
BACKGROUND
Mechanisms of neuroprotection encompass energy deficits in brain arising from insufficient oxygen and glucose levels following respiratory failure; ischemia or stroke, which produce metabolic stresses that lead to unconsciousness and seizures; and the effects of general anesthetics. Foremost among those K(+) channels viewed as important for neuroprotection are ATP-sensitive (K(ATP)) channels, which belong to the family of inwardly rectifying K(+) channels (K(ir)) and contain a sulfonylurea subunit (SUR1 or SUR2) combined with either K(ir)6.1 (KCNJ8) or K(ir)6.2 (KCNJ11) channel pore-forming alpha-subunits, and various members of the tandem two-pore or background (K(2P)) K(+) channel family, including K(2P)1.1 (KCNK1 or TWIK1), K(2P)2.1 (KCNK2 or TREK/TREK1), K(2P)3.1 (KCNK3 or TASK), K(2P)4.1 (KCNK4 or TRAAK), and K(2P)10.1 (KCNK10 or TREK2).
OBJECTIVE
This review covers patents and patent applications related to inventions of therapeutics, compound screening methods and diagnostics, including K(ATP) channel openers and blockers, as well as K(ATP) and K(2P) nucleic/amino acid sequences and proteins, vectors, transformed cells and transgenic animals. Although the focus of this patent review is on brain and neuroprotection, patents covering inventions of K(ATP) channel openers for cardioprotection, diabetes mellitus and obesity, where relevant, are addressed.
CONCLUSIONS
Overall, an important emerging therapeutic mechanism underlying neuroprotection is activation/opening of K(ATP) and K(2P) channels. To this end substantial progress has been made in identifying and patenting agents that target K(ATP) channels. However, current K(2P) channels patents encompass compound screening and diagnostics methodologies, reflecting an earlier 'discovery' stage (target identification/validation) than K(ATP) in the drug development pipeline; this reveals a wide-open field for the discovery and development of K(2P)-targeting compounds.
