Cited by We are MedChem: The Frontiers in Medicinal Chemistry 2024

Discovery of a Small Molecule Activator of Slack (Kcnt1) Potassium Channels That Significantly Reduces Scratching in Mouse Models of Histamine‐Independent and Chronic Itch DOI

Annika Balzulat,

Wenyong Zhu,

Cathrin Flauaus

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(15)

Published: Feb. 13, 2024

Abstract Various disorders are accompanied by histamine‐independent itching, which is often resistant to the currently available therapies. Here, it reported that pharmacological activation of Slack (Kcnt1, K Na 1.1), a potassium channel highly expressed in itch‐sensitive sensory neurons, has therapeutic potential for treatment itching. Based on Slack‐activating antipsychotic drug, loxapine, series new derivatives with improved pharmacodynamic and pharmacokinetic profiles designed enables validate as target vivo. One these activators, compound 6, exhibits negligible dopamine D 2 3 receptor binding, unlike loxapine. Notably, 6 displays potent on‐target antipruritic activity multiple mouse models acute chronic itch without motor side effects. These properties make lead molecule development therapies targeting Slack.

Language: Английский

Citations

Physiological Implications of the Slack Channel in the Central and Peripheral Nervous Systems DOI

Zhen Li, Aqeela Zahra,

Zhongyu Wang

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177482 - 177482

Published: March 1, 2025

Language: Английский

Citations

A Novel Smart Hydrogel Strain Sensor for Efficient and Quantitative Detection of Blood Potassium Concentration with a Drop of Serum DOI

Jun Yao, Han Fu,

Y Xia

et al.

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Abstract Quantitative detection of potassium ion (K + ) concentration in serum is great significance for clinical diagnosis and management. Although various methods are developed quantitative K concentration, the existed techniques often fall short realization rapid with small volume sample. Here, a novel smart hydrogel strain sensor that combines poly( N ‐isopropylacrylamide‐ co ‐benzo‐15‐crown‐5‐acrylamide) (PNB) resistance gauge efficient by converting amplifying biochemical signals into easily measurable variations. By rationally regulating PNB hydrogels crosslinked Laponite XLG nanosheets, sensors can be rapidly achieved 2 min. Because sensitive transformation enables measurement extremely slight deformation hydrogels, only one drop 16 µL required to achieve blood sensors. The exhibit exceptional interference repeated performances. proposed strategy not offers method concentrations, but also opens up new window developing applications.

Language: Английский

Citations

Slack K+ channels confer protection against myocardial ischemia/reperfusion injury DOI

Anna Roslan,

Katharina Paulus,

Jiaqi Yang

et al.

Cardiovascular Research, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 5, 2024

Abstract Aims Na+-activated Slack potassium (K+) channels are increasingly recognized as regulators of neuronal activity, yet little is known about their role in the cardiovascular system. activity increases when intracellular Na+ concentration ([Na+]i) reaches pathophysiological levels. Elevated [Na+]i a major determinant ischaemia and reperfusion (I/R)-induced myocardial injury; thus, we hypothesized that plays under these conditions. Methods results K+ currents cardiomyocytes (CMs) obtained from wildtype but not global knockout mice were sensitive to electrical inactivation voltage-sensitive channels. Live-cell imaging demonstrated fluxes across sarcolemma rely on Slack, while depolarized resting membrane potential Slack-deficient CMs led excessive cytosolic Ca2+ accumulation finally hypoxia/reoxygenation-induced cell death. Cardiac damage an vivo model I/R was exacerbated CM-specific conditional mutants largely insensitive mechanical conditioning manoeuvres. Finally, protection conferred by mitochondrial ATP-sensitive (mitoKATP) required functional CMs. Conclusion Collectively, our study provides evidence for Slack's crucial involvement ion homeostasis no or low O2-stressed Thereby, opposes I/R-induced fatal Ca2+-uptake supporting cardioprotective signaling attributed mitoKATP function.

Language: Английский

Citations

The SOSA Approach to Drug Discovery DOI

Norbert Handler,

Michal Pozník,

Helmut Buschmann

et al.

Published: Dec. 27, 2024

Language: Английский

Citations

We are MedChem: The Frontiers in Medicinal Chemistry 2024 DOI

Matthias Schiedel,

Philipp Barbie,

Felix Pape

et al.

ChemMedChem, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 23, 2024

The Frontiers in Medicinal Chemistry (FiMC) is the largest international conference Germany and took place from March 17

Language: Английский

Citations