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

Vyas, Vivek K.; Parikh, Palak K.; Ramani, Jonali; Ghate, Manjunath

doi:10.2174/0929867325666180430152023

Cited by 7 publications

(7 citation statements)

References 74 publications

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“…ampening cellular electrical activity by pharmacological activation of specific types of K + channels has therapeutic potential for the treatment of a variety of disease states, including epilepsy, arrhythmias, vascular constriction, and various pain conditions (1,2). Consequently, screening efforts have identified a number of agents that open different types of K + channels (2), presumably by targeting their respective channel-specific activation mechanisms.…”

mentioning

confidence: 99%

A pharmacological master key mechanism that unlocks the selectivity filter gate in K ⁺ channels

Schewe

Sun

Mert

et al. 2019

Science

112

184

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Potassium (K+) channels have been evolutionarily tuned for activation by diverse biological stimuli, and pharmacological activation is thought to target these specific gating mechanisms. Here we report a class of negatively charged activators (NCAs) that bypass the specific mechanisms but act as master keys to open K+channels gated at their selectivity filter (SF), including many two-pore domain K+(K2P) channels, voltage-gated hERG (human ether-à-go-go–related gene) channels and calcium (Ca2+)–activated big-conductance potassium (BK)–type channels. Functional analysis, x-ray crystallography, and molecular dynamics simulations revealed that the NCAs bind to similar sites below the SF, increase pore and SF K+occupancy, and open the filter gate. These results uncover an unrecognized polypharmacology among K+channel activators and highlight a filter gating machinery that is conserved across different families of K+channels with implications for rational drug design.

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mentioning

confidence: 99%

A pharmacological master key mechanism that unlocks the selectivity filter gate in K ⁺ channels

Schewe

Sun

Mert

et al. 2019

Science

112

184

View full text Add to dashboard Cite

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“…When extracellular K + concentration increasing, it subsequently causes neuronal membrane depolarization (Tang et al., 2010). As the membrane is depolarized in neuronal firing activity, the central ion pore of Kv channels will open for K + efflux, thus drives the membrane potential toward a negative direction, which leads to repolarization in action potential, and finally quiets the cell activity (Vyas et al., 2019; Wu et al., 2015).…”

Section: Genetic Dysfunction Of Potassium Channels and Asd: From Genotypes To Phenotypesmentioning

confidence: 99%

“…It was reported that about 15 Kir clones were identified and classified in seven different families (Kir1 through Kir7) based on their sequence similarities and functional properties (Binda et al., 2018). Kir channel contains two transmembrane regions and a pore‐forming domain, permitting K + to move into the cell and are often regulated by intracellular factors, like ATP‐sensitive potassium channels (Vyas et al., 2019) (see Figure 3). Aberrant Kir channel expression and function may lead to defective brain development and an imbalance of K + homeostasis in the brain, which could finally result in neuropsychiatric and developmental disorders (Sun et al., 2018).…”

Section: Genetic Dysfunction Of Potassium Channels and Asd: From Genotypes To Phenotypesmentioning

confidence: 99%

Potassium channels and autism spectrum disorder: An overview

Cheng

Qiu

2021

Intl J of Devlp Neuroscience

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Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by impaired social interaction and communication, and restricted, repetitive patterns of behaviors, interests, or activities. It had been demonstrated that potassium channels played a key role in regulating neuronal excitability, which was closely associated with neurological diseases including epilepsy, ataxia, myoclonus, and psychiatric disorders. In recent years, a growing body of evidence from whole‐genome sequencing and whole‐exome sequencing had identified several ASD susceptibility genes of potassium channels in ASD subjects. Genetically dysfunction of potassium channels may be involved in altered neuronal excitability and abnormal brain function in the pathogenesis of ASD. This review summarizes current findings on the features of ASD‐risk genes (KCND2, KCNQ2, KCNQ3, KCNH5, KCNJ2, KCNJ10, and KCNMA1) and further expatiate their potential role in the pathogenicity of ASD.

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“…Bai found that over-expression of miR (short non-coding RNA molecules)À296-3p sensitised glioblastoma cells to anticancer drugs, whereas downexpression using antisense oligonucleotides conferred MDR (Bai et al, 2013). Meanwhile, it has been found that a large number of toxins and drugs have the ability to regulate K þ channels, which can be used to block K þ channels or change channels' sensitivities to voltage and calcium concentration (Vyas et al, 2019).…”

Section: Blockers Of K þ Channel and Treatments Of Gliomasmentioning

confidence: 99%

Potassium channels and their role in glioma: A mini review

Liu

Han

et al. 2019

Molecular Membrane Biology

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K þ channels regulate a multitude of biological processes and play important roles in a variety of diseases by controlling potassium flow across cell membranes. They are widely expressed in the central and peripheral nervous system. As a malignant tumor derived from nerve epithelium, glioma has the characteristics of high incidence, high recurrence rate, high mortality rate, and low cure rate. Since glioma cells show invasive growth, current surgical methods cannot completely remove tumors. Adjuvant chemotherapy is still needed after surgery. Because the blood-brain barrier and other factors lead to a lower effective concentration of chemotherapeutic drugs in the tumor, the recurrence rate of residual lesions is extremely high. Therefore, new therapeutic methods are needed. Numerous studies have shown that different K þ channel subtypes are differentially expressed in glioma cells and are involved in the regulation of the cell cycle of glioma cells to arrest them at different stages of the cell cycle. Increasing evidence suggests that K þ channels express in glioma cells and regulate glioma cell behaviors such as cell cycle, proliferation and apoptosis. This review article aims to summarize the current knowledge on the function of K þ channels in glioma, suggests K þ channels participating in the development of glioma.

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

Abstract: 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.

Cited by 7 publications

References 74 publications

A pharmacological master key mechanism that unlocks the selectivity filter gate in K ⁺ channels

A pharmacological master key mechanism that unlocks the selectivity filter gate in K ⁺ channels

Potassium channels and autism spectrum disorder: An overview

Potassium channels and their role in glioma: A mini review

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

Abstract: 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.

Cited by 7 publications

References 74 publications

A pharmacological master key mechanism that unlocks the selectivity filter gate in K + channels

A pharmacological master key mechanism that unlocks the selectivity filter gate in K + channels

Potassium channels and autism spectrum disorder: An overview

Potassium channels and their role in glioma: A mini review

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Product

Resources

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A pharmacological master key mechanism that unlocks the selectivity filter gate in K ⁺ channels

A pharmacological master key mechanism that unlocks the selectivity filter gate in K ⁺ channels