The shifting landscape of KATP channelopathies and the need for ‘sharper’ therapeutics
Identifieur interne : 000993 ( Main/Exploration ); précédent : 000992; suivant : 000994The shifting landscape of KATP channelopathies and the need for ‘sharper’ therapeutics
Auteurs : Sujay V. Kharade [États-Unis] ; Colin Nichols [États-Unis] ; Jerod S. Denton [États-Unis]Source :
- Future Medicinal Chemistry [ 1756-8919 ] ; 2016.
Abstract
ATP-sensitive potassium (KATP) channels play fundamental roles in the regulation of endocrine, neural and cardiovascular function. Small-molecule inhibitors (e.g., sulfonylurea drugs) or activators (e.g., diazoxide) acting on SUR1 or SUR2 have been used clinically for decades to manage the inappropriate secretion of insulin in patients with Type 2 diabetes, hyperinsulinism and intractable hypertension. More recently, the discovery of rare disease-causing mutations in KATP channel-encoding genes has highlighted the need for new therapeutics for the treatment of certain forms of neonatal diabetes mellitus, congenital hyperinsulinism and Cantu syndrome. Here, we provide a high-level overview of the pathophysiology of these diseases and discuss the development of a flexible high-throughput screening platform to enable the development of new classes of KATP channel modulators.
Url:
DOI: 10.4155/fmc-2016-0005
PubMed: 27161588
PubMed Central: 4976861
Affiliations:
- États-Unis
- Missouri (État)
- Saint-Louis (Missouri)
- École de médecine (Université Washington de Saint-Louis)
Links toward previous steps (curation, corpus...)
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- to stream Ncbi, to step Checkpoint: 008262
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- to stream Main, to step Curation: 000993
Le document en format XML
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<front><div type="abstract" xml:lang="en"><p>ATP-sensitive potassium (K<sub>ATP</sub>
) channels play fundamental roles in the regulation of endocrine, neural and cardiovascular function. Small-molecule inhibitors (e.g., sulfonylurea drugs) or activators (e.g., diazoxide) acting on SUR1 or SUR2 have been used clinically for decades to manage the inappropriate secretion of insulin in patients with Type 2 diabetes, hyperinsulinism and intractable hypertension. More recently, the discovery of rare disease-causing mutations in K<sub>ATP</sub>
channel-encoding genes has highlighted the need for new therapeutics for the treatment of certain forms of neonatal diabetes mellitus, congenital hyperinsulinism and Cantu syndrome. Here, we provide a high-level overview of the pathophysiology of these diseases and discuss the development of a flexible high-throughput screening platform to enable the development of new classes of K<sub>ATP</sub>
channel modulators.</p>
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