scholarly journals Chemical modulation of Kv7 potassium channels

2021 ◽  
Author(s):  
Matteo Borgini ◽  
Pravat Mondal ◽  
Ruiting Liu ◽  
Peter Wipf
Keyword(s):  
Potassium Channels ◽  
Small Molecule ◽  
Medicinal Chemistry ◽  
Voltage Gated ◽  
Chemical Modulation ◽  
Small Molecule Modulators

This review describes the synthetic and medicinal chemistry of small molecule modulators of the voltage-gated Kv7 (KCNQ) potassium channels and the available data of their biological and clinical properties.

Medicinal Chemistry of Potassium Channel Modulators: An Update of Recent Progress (2011-2017)

2019 ◽  
Vol 26 (12) ◽  
pp. 2062-2084 ◽  
Author(s):  
Vivek K. Vyas ◽  
Palak Parikh ◽  
Jonali Ramani ◽  
Manjunath Ghate
Keyword(s):  
Potassium Channels ◽  
Potassium Channel ◽  
Small Molecule ◽  
Medicinal Chemistry ◽  
Hormone Secretion ◽  
K Channel ◽  
Biological Functions ◽  
Chemistry Research ◽  
Channel Inhibition ◽  
Potassium Channel Modulators

Background: Potassium (K+) channels participate in many physiological processes, cardiac function, cell proliferation, neuronal signaling, muscle contractility, immune function, hormone secretion, osmotic pressure, changes in gene expression, and are involved in critical biological functions, and in a variety of diseases. Potassium channels represent a large family of tetrameric membrane proteins. Potassium channels activation reduces excitability, whereas channel inhibition increases excitability. Objective: Small molecule K+ channel activators and inhibitors interact with voltage-gated, inward rectifying, and two-pore tandem potassium channels. Due to their involvement in biological functions, and in a variety of diseases, small molecules as potassium channel modulators have received great scientific attention. Methods: : In this review, we have compiled the literature, patents and patent applications (2011 to 2017) related to different chemical classes of potassium channel openers and blockers as therapeutic agents for the treatment of various diseases. Many different chemical classes of selective small molecule have emerged as potassium channel modulators over the past years. Conclusion: This review discussed the current understanding of medicinal chemistry research in the field of potassium channel modulators to update the key advances in this field.

scholarly journals Development of Allosteric Modulators of Voltage-Gated Na+ Channels: A Novel Approach for an Old Target

2021 ◽  
Vol 21 ◽  
Author(s):  
Nolan M. Dvorak ◽  
Paul A. Wadsworth ◽  
Pingyuan Wang ◽  
Jia Zhou ◽  
Fernanda Laezza
Keyword(s):  
Ion Channels ◽  
Small Molecules ◽  
Small Molecule ◽  
Sequence Divergence ◽  
Specific Protein ◽  
Allosteric Modulators ◽  
Α Subunit ◽  
Voltage Gated ◽  
Nav Channels ◽  
Small Molecule Modulators

: Given their primacy in governing the action potential (AP) of excitable cells, voltage-gated Na+ (Nav) channels are important pharmacological targets of therapeutics for a diverse array of clinical indications. Despite historically being a traditional drug target, therapeutics targeting Nav channels lack isoform selectivity, giving rise to off-target side effects. To develop isoform-selective modulators of Nav channels with improved target-specificity, the identification and pharmacological targeting of allosteric sites that display structural divergence among Nav channel isoforms represents an attractive approach. Despite the high homology among Nav channel α subunit isoforms (Nav1.1-Nav1.9), there is considerable amino acid sequence divergence among their constituent C-terminal domains (CTD), which enables structurally and functionally specific protein: protein interaction (PPI) with auxiliary proteins. Although pharmacological targeting of such PPI interfaces between the CTDs of Nav channels and auxiliary proteins represents an innovate approach for developing isoform-selective modulators of Nav channels, appreciable modulation of PPIs using small molecules has conventionally been difficult to achieve. After briefly discussing the challenges of modulating PPIs using small molecules, this current frontier review that follows subsequently expounds on approaches for circumventing such difficulties in the context of developing small molecule modulators of PPIs between transmembrane ion channels and their auxiliary proteins. In addition to broadly discussing such approaches, the implementation of such approaches is specifically discussed in the context of developing small molecule modulators between the CTD of Nav channels and auxiliary proteins. Developing allosteric modulators of ion channels by targeting their PPI interfaces with auxiliary proteins represents an innovative and promising strategy in ion channel drug discovery that could expand the “druggable genome” and usher in first-in-class PPI-targeting therapeutics for a multitude of channelopathies.

scholarly journals Presynaptic Paraneoplastic Disorders of the Neuromuscular Junction: An Update

2021 ◽  
Vol 11 (8) ◽  
pp. 1035
Author(s):  
Maria Pia Giannoccaro ◽  
Patrizia Avoni ◽  
Rocco Liguori
Keyword(s):  
Potassium Channels ◽  
Neuromuscular Junction ◽  
Calcium Channels ◽  
Myasthenia Gravis ◽  
Neuromuscular Transmission ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Immune Mediated ◽  
Recent Developments ◽  
Myasthenic Syndrome

The neuromuscular junction (NMJ) is the target of a variety of immune-mediated disorders, usually classified as presynaptic and postsynaptic, according to the site of the antigenic target and consequently of the neuromuscular transmission alteration. Although less common than the classical autoimmune postsynaptic myasthenia gravis, presynaptic disorders are important to recognize due to the frequent association with cancer. Lambert Eaton myasthenic syndrome is due to a presynaptic failure to release acetylcholine, caused by antibodies to the presynaptic voltage-gated calcium channels. Acquired neuromyotonia is a condition characterized by nerve hyperexcitability often due to the presence of antibodies against proteins associated with voltage-gated potassium channels. This review will focus on the recent developments in the autoimmune presynaptic disorders of the NMJ.

scholarly journals Small-molecule modulators of inward rectifier K+channels: recent advances and future possibilities

2010 ◽  
Vol 2 (5) ◽  
pp. 757-774 ◽  
Author(s):  
Gautam Bhave ◽  
Daniel Lonergan ◽  
Brian A Chauder ◽  
Jerod S Denton
Keyword(s):  
Small Molecule ◽  
Inward Rectifier ◽  
K Channels ◽  
Recent Advances ◽  
Small Molecule Modulators
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