Potassium Channel Activator

Chlorzoxazone is a SK-type potassium channel activator. Chlorzoxazone modulates FOXO3 phosphorylation and Aβ. Chlorzoxazone enhances immunosuppression, attenuates vasoconstriction, attenuates cognitive deficits, and improves experimental autoimmune encephalomyelitis.

ML277 (CID-53347902) is a potent and selective activator of K(v)7.1 (KCNQ1) potassium channel activator (EC₅₀=270 nM), rescues function of pathophysiologically important mutant channel complexes in human induced pluripotent stem cell-derived cardiomyocytes.

Flupirtine (D 9998) Maleate is an orally active, blood-brain barrier-crossing non-opioid analgesic and neuroprotective agent. Flupirtine Maleate is a neuronal potassium channel opener (Kv7 activator), a NMDA receptor antagonist and a GABA receptor activator. Flupirtine Maleate stabilizes blood-brain-barrier integrity, reduces oxidative stress and brain leukocyte infiltration, enhances angioneurogenesis, suppresses calcium influx, stabilizes neuronal resting membrane potential, and counteracts focal cerebral ischemia. Flupirtine Maleate exhibits analgesic, muscle relaxant properties, protects neurons from excitotoxic, ischemic, or cytokine-mediated death. Flupirtine Maleate functions as a non-opioid analgesic without antipyretic or antiphlogistic properties, shows no relevant affinity to opiate receptor. Flupirtine Maleate can be used for the research of focal cerebral ischemia, pain, Alzheimer’s disease, or multiple sclerosis.

NS309 is a potent and selective activator of the Ca²⁺-activated SK/IK potassium channels, but displays no activity at BK channels.

CLP290 is an orally available activator of the neuron-specific K⁺-Cl^- cotransporter KCC2, displays potential for treatment of a wide range of neurological and psychiatric indications. CLP290 can significantly lower blood arginine-vasopressin (AVP) and glucose levels in STZ (HY-13753) rats.

ICA-27243 is a selective, potent and orally active KCNQ2/Q3 potassium channel opener with an EC₅₀ of 0.38 μM. ICA-27243 is less effective at activating KCNQ4 and KCNQ3/Q5. ICA-27243 has antiepileptic and anticonvulsant effects.

Minocycline is an orally active, potent and BBB-penetrated semi-synthetic tetracycline antibiotic. Minocycline is a hypoxia-inducible factor (HIF)-1α inhibitor. Minocycline shows anti-cancer, anti-inflammatory, and glutamate antagonist effects. Minocycline reduces glutamate neurotransmission and shows neuroprotective properties and antidepressant effects. Minocycline inhibits bacterial protein synthesis through binding with the 30S subunit of the bacterial ribosome, resulting in a bacteriostatic effect.

Procainamide (Procaine amide) is a specific and potent inhibitor of DNA methyltransferase 1 (DNMT1), which reactivates the expression of tumor suppressor factors by demethylating tumor suppressor genes. Procainamide induces vacuolization in various cell types and reduces cell proliferation and migration. Procainamide relaxes airway smooth muscle by activating potassium channels. Procainamide can be used in cancer and arrhythmia research.

NS 11021 is a potent and specific Ca²⁺-activated big-conductance K⁺ Channels (KCa1.1 channels) activator. NS 11021 at concentrations above 0.3 μM activates KCa1.1 in a concentration-dependent manner by parallelshifting the channel activation curves to more negative potentials.

CLP257 is a selective K⁺-Cl cotransporter KCC2 activator with an EC₅₀ of 616 nM. CLP257 is inactive against NKCC1, GABAA receptors, KCC1, KCC3 or KCC4. CLP257 restores impaired Cl transport in neurons with diminished KCC2 activity. CLP257 alleviates hypersensitivity in rats with neuropathic pain. CLP257 modulates plasmalemmal KCC2 protein turnover post-translationally.

Levcromakalim ((-)-Cromakalim) is an ATP-sensitive K⁺ channel (K_ATP) activator.

Uridine 5'-monophosphate (5'-Uridylic acid) disodium salt is an orally active mitochondrial ATP-dependent potassium channel activator that has a protective effect on the heart. Uridine 5'-monophosphate disodium salt can promote the synthesis of CDP-choline and induce apoptosis in intestinal epithelial cells, which is beneficial for gut development and reduces diarrhea.

BL-1249 is a nonsteroidal anti-inflammatory agent (NSAID) and a potassium channel activator. BL-1249 potently activates K_2P2.1 (TREK-1) and K_2P10.1 (TREK-2) with EC₅₀ values of 5.5 μM and 8.0 μM, respectively. BL-1249 extracellular application activates all TREK subfamily members but has no effect on other K_2P subfamilies. BL-1249 exhibits more selective for the bladder (EC₅₀ of 1.26 μM) than vascular tissue (EC₅₀ of 21.0 μM).

NS-1619 is an opener of large conductance Ca²⁺-activated K⁺ (BK) channel. NS-1619 is a highly effective relaxant with an EC₅₀ of about 10 – 30 μM in several smooth muscles of blood vessels and other tissues. NS1619 inhibits proliferation and induces apoptosis in A2780 ovarian cancer cells.

ML213 is a selective activator of Kv7.2 and Kv7.4 channels, enhances Kv7.2 and Kv7.4 channels with EC₅₀s of 230 and 510 nM, respectively.

ML 297 (VU 0456810) is a potent and selective GIRK_1/2 activator, with an EC₅₀ of 0.16 μM. ML 297 can cross the blood-brain barrier with brain-to-plasma ratio of 0.2 in mice model (i.p.). ML 297 is potential for the treatment of epilepsy.

Nicorandil (SG-75) is a potent potassium channel activator and targets vascular nucleoside diphosphate-dependent K⁺ channels and cardiac ATP-sensitive K⁺ channels (K_ATP). Nicorandil is a nicotinamide ester with vasodilatory and cardioprotective effects and has the potential for angina and forischemic heart diseases.

NS1643 is a partial agonist of human ether-a-go-go-related gene (hERG) K⁺ channels with an EC₅₀ of 10.5 μM. NS1643 inhibits the growth of breast cancer tumors in TNBC mouse models. NS1643 inhibits cell migration and invasion of breast cancer cells.

Rimtuzalcap (CAD-1883) is a first-in-class selective positive allosteric modulator of small-conductance calcium-activated potassium channels (SK channels). Rimtuzalcap can be used for the research of movement disorders including essential tremor (ET) and spinocerebellar ataxia (SCA).

(±)-Naringenin is an orally available anti-inflammatory agent that can regulate both acute and chronic inflammation responses, while also showing antioxidant, neuroprotective, liver-protective, and anti-cancer effects. (±)-Naringenin promotes vasodilation in endothelial cells by activating BK_Ca channels in muscle cells. It also exerts protective effects against experimental colitis by inhibiting Toll-like receptor 4/NF-κB signaling, making it useful in studies related to sepsis, fulminant hepatitis, fibrosis, and cancer research.