Bristol-myers Squibb Compnay

Bristol-myers Squibb

Steven Dworetzky

Valentin K Gribkoff

Piyasena Hewawasam

Gene G Kinney

Pierre Dextraze

Yong-Jin Wu

Chandra S Ramanathan

Jie Chen

Wen-Pin Yang

Michael A Blanar

Alexandre L'Heureux

Paul Charles Levesque

Huan He

Michael G Neubauer

Jean-Paul Daris

Wayne A Little

Li-Quang Sun

Joanne T Trojnacki

The present invention relates to KCNQ proteins defining potassium channels. In particular, the invention concerns the human KCNQ2, human KCNQ3, murine KCNQ2, and rat KCNQ2 proteins reported herein. KCNQ2 and KCNQ3 proteins are nervous system-selective and may be involved in neurotransmission and neuroprotection. The KCNQ2 and KCNQ3 of the present invention can be used to assay for modulators of the proteins, which would be useful in treatment of such disorders as ataxia, myokymia, seizures, Alzheimer's disease, Parkinson's disease, age-associated memory loss, learning deficiencies, motor neuron diseases, epilepsy, stroke, and the like.

DNA encoding rodent KCNQ2 potassium channel

An isolated polynucleotide encoding a novel potassium channel polypeptide, KCNQ5, that is expressed primarily in brain and skeletal muscle is described. The new polypeptide has been cloned and isolated from a human brain cDNA library and is a member the KCNQ family of potassium channels. The provided human KCNQ5 nucleic acid sequence and encoded polypeptide can be employed for diagnostic, screening and therapeutic uses. Moreover, the hKCNQ5 polypeptide can be used to assay for KCNQ5 potassium channel modulators, which can be utilized in the treatment of neurological, neurophysiological, neuropsychological and neuroaffective diseases, conditions and disorders, including, but not limited to, acute and chronic pain, migraine, acute stroke, dementia, vascular dementia, trauma, epilepsy, amyelotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson's Disease, learning and cognitive disorders, and neurophysiological disorders including anxiety disorders, depression, bipolar disorders, sleep disorders, addiction, and eating disorders.

Human kcnq5 potassium channel, methods and compositions thereof

Compounds which function as modulators, particularly, openers, of human KCNQ potassium channel proteins or polypeptides, particularly, central nervous system (CNS)-located KCNQ potassium channels, and heteromultimers thereof, and their use in the treatment of migraine are provided by the present invention. One novel type of potassium channel polypeptide openers provided by the present invention is the fluorooxindole compounds, described for the first time as therapeutics for the treatment of migraine by preventing the asynchronous firing of neurons. Other KCNQ potassium channel opener compounds that are also useful in the treatments of the invention include 2,4-disubstituted pyrimidine-5-carboxamide derivatives. One or more of the compounds according to the present invention may be utilized alone, in combination, or in conjunction with other treatment modalities for reducing, ameliorating and/or alleviating migraine or diseases similar to, or mechanistically related to, migraine, e.g., cluster headache.

3-fluoro-2-oxindole modulators of KCNQ potassium channels and use thereof in treating migraine and mechanistically related disease

Cinnamide derivatives as KCNQ potassium channel modulators

Fluoro oxindole derivatives as modulators if KCNQ potassium channels

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Middlefield, CT, United States of America

Steven Dworetzky