TRPV4 channel is involved in HSV-2 infection in human vaginal epithelial cells through triggering Ca oscillation.

Herpes simplex virus (HSV) infection induces a rapid and transient increase in intracellular calcium concentration ([Ca]), which plays a critical role in facilitating viral entry. T-type calcium channel blockers and EGTA, a chelate of extracellular Ca, suppress HSV-2 infection. But the cellular mechanisms mediating HSV infection-activated Ca signaling have not been completely defined.

Total Ginsenoside Extract from Panax ginseng Enhances Neural Stem Cell Proliferation and Neuronal Differentiation by Inactivating GSK-3β.

Objective: To study the effects of total ginsenosides (TG) extract from Panax ginseng on neural stem cell (NSC) proliferation and differentiation and their underlying mechanisms.

Methods: The migration of NSCs after treatment with various concentrations of TG extract (50, 100, or 200 µ g/mL) were monitored. The proliferation of NSCs was examined by a combination of cell counting kit-8 and neurosphere assays.

ML365 inhibits TWIK2 channel to block ATP-induced NLRP3 inflammasome.

Dysregulation of NLRP3 inflammasome results in uncontrolled inflammation, which participates in various chronic diseases. TWIK2 potassium channel mediates potassium efflux that has been reported to be an essential upstream mechanism for ATP-induced NLRP3 inflammasome activation. Thus, TWIK2 potassium channel could be a potential drug target for NLRP3-related inflammatory diseases.

CDER167, a dual inhibitor of URAT1 and GLUT9, is a novel and potent uricosuric candidate for the treatment of hyperuricemia.

Urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) are important targets for the development of uric acid-lowering drugs. We previously showed that the flexible linkers of URAT1 inhibitors could enhance their potency. In this study we designed and synthesized CDER167, a novel RDEA3710 analogue, by introducing a linker (methylene) between the naphthalene and pyridine rings to increase flexibility, and characterized its pharmacological and pharmacokinetics properties in vitro and in vivo.

Identification and characterization of a series of novel HCN channel inhibitors.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a critical role in controlling pacemaker activity in both heart and nervous system. Developing HCN channel inhibitors has been proposed to be an important strategy for the treatment of pain, heart failure, arrhythmias, and epilepsy. One HCN channel inhibitor, ivabradine, has been clinically approved for the treatment of angina pectoris and heart failure.

Discovery of a retigabine derivative that inhibits KCNQ2 potassium channels.

Aim: Retigabine, an activator of KCNQ2-5 channels, is currently used to treat partial-onset seizures. The aim of this study was to explore the possibility that structure modification of retigabine could lead to novel inhibitors of KCNQ2 channels, which were valuable tools for KCNQ channel studies.

Methods: A series of retigabine derivatives was designed and synthesized.

Comparison of the effects of DC031050, a class III antiarrhythmic agent, on hERG channel and three neuronal potassium channels.

Aim: This study was conducted to test the selectivity of DC031050 on cardiac and neuronal potassium channels.

Methods: Human ether-à-go-go related gene (hERG), KCNQ and Kv1.2 channels were expressed in CHO cells.

Activation of human ether-a-go-go related gene (hERG) potassium channels by small molecules.

Human ether-a-go-go related gene (hERG) potassium (K(+)) channels play a critical role in cardiac action potential repolarization. Mutations that reduce hERG conductance or surface expression may cause congenital long QT syndrome (LQTS). However, the channels can be inhibited by structurally diverse small molecules, resulting in an acquired form of LQTS.