Potassium Channel Activator

NS5806, a potent potassium current activator, increases K_V4.3/KChIP2 peak current amplitudes with an EC₅₀ of 5.3 μM. NS5806 slows K_V4.3 and K_V4.2 current dacay in channel complexes containing KChIP2.

KB130015 (KB015) is an orally active and potent ThRα and ThRβ (thyroid hormone receptor) inhibitor, with IC₅₀ values of 4.5 and 5.1 μM, respectively. KB130015 markedly slows the kinetics of inactivation of Na⁺ channels. KB130015 activates hERG1 channels (EC₅₀ = 12.2 μM) and large-conductance Ca²⁺-activated K⁺ (BKCa) channels formed by hSlo1 (α) subunits in HEK 293 cells. KB130015 has antiarrhythmic properties. KB130015 can be used for the study of cardiovascular disease.

Opakalim (BHV-7000) is a selective Kv7.2/7.3 potassium channels activator with an EC₅₀ of 0.6 μM. Opakalim shows minimal GABAA receptor activation and exhibits potent anti-seizure efficacy in the maximal electroshock seizure (MES) model. Opakalim can be used for the study of seizures.

ML335 is a selective activator of both TREK-1 and TREK-2.

ML402, a thiophene-carboxamide, is a selective K_2P2.1(TREK-1) and K_2P10.1(TREK-2) activator. ML402 is inactive against K_2P4.1(TRAAK).

L-364,373 (R-L3) is a voltage-gated Kv7.1 (KCNQ1)/mink channels activator. L-364,373 activates Iks (slow delayed rectifier potassium current) and shortens action potential duration in guinea pig cardiac myocytes, and suppresses early afterdepolarizations in rabbit ventricular myocytes.

Cinnamyl Alcohol is an active component from chestnut flower, inhibits increased PPARγ expression, exhibits anti-obesity, antioxidant and anti-inflammatory activities.

Tifenazoxide (NN414) is a potent, orally active and SUR1/Kir6.2 selective K^ATP channels opener. Tifenazoxide has antidiabetic effect, can inhibit glucose stimulated insulin release in vitro and in vivo, and has a beneficial effect on glucose homeostasis.

P-1075 is a potent activator of sulfonylurea receptor 2-associated ATP-sensitive potassium channels (SUR2-K_IR6), with an EC₅₀ value of 45 nM for SUR2B-K_IR6 channel activation. P-1075 also P1075 opens mitochondrial K(ATP) channels and generates reactive oxygen species resulting in cardioprotection of rabbit hearts.

CyPPA is a positive modulator of hSK3 and hSK2, with EC₅₀ values of 14 μM and 5.6 μM, repectively. CyPPA is inactive on both hSK1 and hIK channels^[1]

SKA-31 is a potent potassium channel activator with EC_50s of 260 nM, 1.9 μM, 2.9 μM, and 2.9 μM for KCa3.1, KCa2.2, KCa2.1 and KCa2.3, respectively. SKA-31 potentiates endothelium-derived hyperpolarizing factor response and lowers blood pressure.

Dibutyryl-cGMP sodium (Bt2cGMP sodium) is a cell-permeable cGMP analogue. Dibutyryl-cGMP sodium preferentially activates cGMP-dependent protein kinase (PKG). Dibutyryl-cGMP sodium inhibits the release of [³H]-arachidonic acid from γ thrombin-stimulated human platelets. Dibutyryl-cGMP sodium induces peripheral antinociception via activation of ATP-sensitive K⁺ channels.

Tenidap (CP-66248) is an orally active dual inhibitor of 5-LOX and COX with anti-inflammatory and immunomodulatory properties. Tenidap downregulates the expression of IL-1 receptors in chondrocytes, reduces the release of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-α, and inhibits MMP production and cartilage degradation. Tenidap also blocks bone resorption and leukocyte adhesion to vascular endothelium, interferes with ion and pH changes associated with mouse sperm capacitation, and selectively enhances the activity of hKir2.3 channels (EC₅₀=1.3 μM). Tenidap is applicable to research related to rheumatoid arthritis.

GI-530159 is a selective opener of TREK1 and TREK2 potassium channels. GI-530159 displays selectivity for TREK1/2 over TRAAK, TASK3 and other potassium channels, with an EC₅₀ of 0.76 μM for TREK1. GI-530159 reduces rat dorsal root ganglion neuron excitability and shows potential analgesic effect.

BMS 191011 (BMS-A) is a potent BK_Ca channel opener (large-conductance Ca²⁺-activated potassium channel). BMS-191011 shows neuroprotective activities in rodent models of stroke.

SKA-121 is a selective K_Ca3.1 activator. SKA-121 exhibits EC₅₀s of 109 nM and 4.4 μM for K_Ca3.1 and K_Ca2.3, respectively.

S-D-Lactoylglutathione (S-Lactylglutathione; (R)-S-Lactoylglutathione) is a multifunctional metabolic intermediate of the glyoxalase system. S-D-Lactoylglutathione activates K⁺ efflux in bacteria by displacing inhibitory glutathione from KefGB channels, thereby acidifying the cytoplasm. In eukaryotic cells, S-D-Lactoylglutathione mediates S-glutathionylation as a substrate of glyoxalase 2. S-D-Lactoylglutathione serves as a sensitive metabolic biomarker for neodymium nitrate neurotoxicity; when used in combination with MSCs-exo, it upregulates glutathione levels, downregulates lactate dehydrogenase and Glo2 levels, and inhibits cellular inflammatory responses and pyroptosis. S-D-Lactoylglutathione can be used in research related to prostate cancer, breast cancer, non-small cell lung cancer, sepsis-associated encephalopathy, and neurotoxicity.

ONO-2920632 is an orally active and central nervous system (CNS)-penetrant TREK activator, with EC₅₀ values of 0.3 µM and 2.8 μM for TREK-1 and TREK-2, respectively. ONO-2920632 exhibits selectivity for other K2P channels (>91-fold selective versus TASK1, TASK2, TASK3, TRAAK, and TWIK2; 31-fold selective versus TRESK). ONO-2920632 possesses analgesic effects and can be used in research on pain, migraine, and neurological disorders.

ICA-069673 is a KCNQ2/Q3 potassium channel activator. ICA-069673 demonstrates greater selectivity for KV7.2/7.3 over KV7.3/KV7.5, with EC₅₀s of 0.69 μM and 14.3 μM, respectively. ICA-069673 inhibits spontaneous phasic and nerve-evoked contractions in guinea pig detrusor smooth muscle (DSM). ICA-069673 also decreases the global intracellular Ca(2+) concentration in DSM cells.

RPR-260243, a potent activator of human ether-a-go-go-related gene (hERG), slows deactivation and attenuates inactivation of hERG1 channels. RPR260243-modified HERG currents are inhibited by Dofetilide (IC₅₀=58 nM). RPR260243 displays no activator-like effects on other voltage-dependent ion channels, including the closely related ERG3 K+ channel. RPR-260243 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.