Glibenclamide(Glyburide) is a sulfonylurea compound that modulates insulin production. IC50 value:Target:Sulfonylureas bind to ATP-dependent K+ channels in beta cells of the pancreas, depolarizing them and stimulating the release of Ca2+, which in turn stimulates insulin production. Glibenclamide, a sulphonylurea oral hypoglycaemic agent is a widely used antagonist of cromakalim-activated K+ channels in smooth muscle. Binding of Gli to SUR produces the closure of KATP channels and the inhibition of their activity. Glibenclamide is widely used for treatment of type 2-diabetes and it has been signaled as antiproliferative in several tumor cell lines.
Margatoxin, an alpha-KTx scorpion toxin, is a high affinity inhibitor of Kv1.3 (Kd=11.7 pM). Margatoxin inhibits the Kv1.2 (Kd=6.4 pM) and Kv1.1 (Kd=4.2 nM). Margatoxin, a 39 amino-acid-long peptide, is isolated from the venom of the scorpion Centruroides margaritatus and widely used in ion channel research[1][2].
P-CAB agent 2 hydrochloride is a potent and orally active potassium-competitive acid blocker and a gastric acid secretion inhibitor. P-CAB agent 2 hydrochloride inhibits H+/K+-ATPase activity with an IC50 value of <100 nM. P-CAB agent 2 hydrochloride inhibits the hERG potassium channel with an IC50 value of 18.69 M. P-CAB agent 2 hydrochloride shows no acute toxicity and inhibits histamine (HY-B1204)-induced gastric acid secretion[1].
4-Aminopyridine is a nonselective K+ channel blocker that binds from the cytoplasmic side of the cell membrane.Target: Potassium Channel4-Aminopyridine(4AP) is a nonselective K+ channel blocker that binds from the cytoplasmic side of the cell membrane. 4AP strongly potentiates transmitter release from the unmyelinated terminals of rat motor nerves, and the possibility arose that demyelinated axon membrane, which can conduct impulses continuously like an unmyelinated fibre, might further resemble its unmyelinated terminals by responding to 4AP. In testing this hypothesis [1]. 4-AP blocked channels from the cytosolic face. 4-AP can both enhance and block Kv1.5 current and suggest that 4-AP can bind with different affinities to more than one site on Kv1.5 channels [2].
(Rac)-Indapamide-d3 is a labelled racemic Indapamide. Indapamide is an orally active sulphonamide diuretic agent, that can reduce blood pressure by decreasing vascular reactivity and peripheral vascular resistance. Indapamide is also can reduce left ventricular hypertrophy[1][4].
ICA-069673 is a KCNQ2/Q3 potassium channel activator with an IC50 of 0.69 μM.
Kaliotoxin is a peptidyl inhibitor of neuronal BK-Type. Kaliotoxin can specific inhibit Kv channels and calcium-activated potassium channels. Kaliotoxin can be used for the research of the regulation of membrane potential and neuron excitability[1][2].
MPO-IN-5 (compound 1) is a potent, irreversible MPO (myeloperoxidase) inhibitor. MPO-IN-5 inhibits MPO peroxidation and hERG binding, with IC50 values of 0.22 and 2.8 μM, respectively. MPO-IN-5 shows rapid kinetics of inhibition, with enzyme inactivation rate (kinact/Ki) of 23000 M−1s−1[1].
Oxypeucedanin is a furocoumarin derivative isolated from Angelica dahurica. Oxypeucedanin is a selective open-channel blocker, inhibits the hKv1.5 current with an IC50 value of 76 nM. Oxypeucedanin prolongs cardiac action potential duration (APD), is a potential antiarrhythmic agent for atrial fibrillation[1]. Oxypeucedanin induces cell apoptosis through inhibition of cancer cell migration[2].
Kv3 modulator 1 is a Kv3 voltage-gated potassium channel modulator extracted from patent WO2018020263A1, Compound X. Kv3 modulator 1 can be used to treat inflammatory pain[1].
UCL 1684 (dibromide) is a first nanomolar, non-peptidic small conductance calcium-activated potassium (SK) channel blocker. UCL 1684 (dibromide) is effective in preventing the development of atrial fibrillation due to potent atrial-selective inhibition of INa. UCL 1684 (dibromide) causes atrial-selective prolongation of ERP secondary to induction of postrepolarization refractoriness[1][2][3].
Endoxifen Z-isomer is the most important Tamoxifen metabolite responsible for eliciting the anti-estrogenic effects of this drug in breast cancer cells expressing estrogen receptor-alpha (ERα). Endoxifen inhibits hERG tail currents at 50 mV in a concentration-dependent manner with IC50 values of 1.6 μM.IC50 value: 1.6 μM [1]Target: hERG Potassium Channel, Estrogen Receptor/ERREndoxifen Z-isomer is considered a prodrug, since it has a much higher potency for the estrogen receptor than its parent drug. Endoxifen inhibits the hERG channel protein trafficking to the plasma membrane in a concentration-dependent manner with Endoxifen being more potent than Tamoxifen. [1] Endoxifen is also shown to be a more potent inhibitor of estrogen target genes when ERβ is expressed. Additionally, low concentrations of Endoxifen Z-isomer observed in Tamoxifen treated patients with deficient CYP2D6 activity (20 to 40 nM) markedly inhibit estrogen-induced cell proliferation rates in the presence of ERβ, whereas much higher Endoxifen Z-isomer concentrations are needed when ERβ is absent.[2]
Daurisoline is a hERG inhibitor and also an autophagy blocker.
Hexachlorophene(Hexachlorofen) is a potent KCNQ1/KCNE1 potassium channel activator with EC50 of 4.61 ± 1.29 μM; also is an inhibitor of Wnt/beta-catenin signaling.IC50 value: 4.61 ± 1.29 μM(EC50) [1]Target: KCNQ1 activatorin vitro: HCP potently increases the current amplitude of KCNQ1/KCNE1 expressed by stabilizing the channel in an open state with an EC(50) of 4.61 ± 1.29 μM. Further studies in cardiomyocytes showed that HCP significantly shortens the action potential duration at 1 μM. In addition, HCP is capable of rescuing the loss of function of the LQTs mutants caused by either impaired activation gating or phosphatidylinositol-4,5-bisphosphate (PIP2) binding affinity [1]. Hexachlorophene antagonized CRT that was stimulated by Wnt3a-conditioned medium by promoting the degradation of beta-catenin. hexachlorophene represses the expression of cyclin D1 [2]. Triclosan and hexachlorophene inhibited both ecFabI and saFabI. hexachlorophene prevented the formation of a stable FabI-NAD(P)(+)-drug ternary complex [3].
L-Palmitoylcarnitine chloride, a long-chain acylcarnitine and a fatty acid metabolite, accumulates in the sarcolemma and deranges the membrane lipid environment during ischaemia. L-Palmitoylcarnitine chloride inhibits KATP channel activity, without affecting the single channel conductance, through interaction with Kir6.2[1].
Rosuvastatin Sodium is a competitive HMG-CoA reductase (HMGCR) inhibitor, with an IC50 of 11 nM. Rosuvastatin Sodium potently blocks hERG current with an IC50 of 195 nM[2]. Rosuvastatin Sodium reduces the expression of the mature hERG and the interaction of heat shock protein 70 (Hsp70) with the hERG protein. Rosuvastatin Sodium effectively lowers low-density lipoprotein (LDL) cholesterol, triglycerides, and C-reactive protein levels[1][2][3].
Pinacidil monohydrate, an antihypertensive drug, is a potassium channel activator.
XE 991 dihydrochloride, a Kv7 (KCNQ) channels blocker, potently inhibits Kv7.1 (KCNQ1), Kv7.2 (KCNQ2), Kv7.2 + Kv7.3 (KCNQ3) channel, and M-current with IC50s of 0.75 µM, 0.71 µM, 0.6 μM, and 0.98 µM, respectively[1].
Amiodarone is an antiarrhythmic drug for inhibition of ATP-sensitive potassium channel with IC50 of 19.1 μM. IC50 Value: 1.5 uM ( inhibit TBARS, LOOH and FPL formation)[1]in vitro: It was found that 10 uM amiodarone induces accumulation of ethidium bromide (5 ug/ml) in Saccharomyces cerevisiae cells. At the same time, in yeast cells with inactivated MDR genes, accumulation of ethidium bromide was 6-fold higher even without amiodarone. Addition of non-lethal concentrations of amiodarone to MDR-deficient cells caused an increase of intracellular ethidium bromide to the level, which was even lower than the level in amiodarone-treated wild-type cells [2]. Cells treated with amiodarone were seen to have detached from the dish, with cell rounding, cytoplasmic blebbing and irregularity in shape. An increase in the sub-G1 phase fraction, from 15.43 to 21.34% and 79.83% and a reduction in the G1 phase fraction, from 48.83 to 41.63% and 11.52%, were observed in cells treated with amiodarone at concentrations of 0.1 and 1 mM, respectively [3].in vivo: Chronic treatment with oral amiodarone for 4 weeks reduced i.p. when myocytes were dialyzed with patch-pipettes containing either 10 mM Na+ or 80 mM Na+. In myocytes from untreated rabbits, acute exposure to amiodarone in vitro reduced i.p. when patch pipettes contained 10 mM Na+ but had no effect on i.p. at 80 mM Na+. Amiodarone had no effect on the voltage dependence of the pump or the affinity of the pump for extracellular K+ either after chronic treatment or during acute exposure [4].Clinical trial: Continuous Versus Episodic Amiodarone Treatment for the Prevention of Permanent Atrial Fibrillation . Phase not specified
8-Azido-ATP, a photoreactable nucleotide analog, is useful for the identification of proteins, such as DNA-dependent RNA polymerase[1].
Chromanol 293B is a selective blocker of the slow delayed rectifier K+ current (IKs) with IC50 of 1-10 μM and a weak inhibitor of KATP channel. Chromanol 293B also blocks the CFTR chloride current with an IC50 of 19 μM[1].
Terfenadine-d3 ((±)-Terfenadine-d3) is the deuterium labeled Terfenadine. Terfenadine ((±)-Terfenadine) is a potent open-channel blocker of hERG with an IC50 of 204 nM[1]. Terfenadine, an H1 histamine receptor antagonist, acts as a potent apoptosis inducer in melanoma cells through modulation of Ca2+ homeostasis. Terfenadine induces ROS-dependent apoptosis, simultaneously activates Caspase-4, -2, -9[2].
A-935142 is a human ether-a-go-go-related gene (hERG, Kv 11.1) channel activator. A-935142 enhances hERG current in a complex manner by facilitation of activation, reduction of inactivation, and slowing of deactivation, and abbreviates atrial and ventricular repolarization[1][2].
PD-118057 is a human ether-a-go-go-related gene (hERG) channel activator that does not cause hERG blockade[1].
SKA-31 is a potent potassium channel activator with EC50s 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[1].
Spadin, a natural peptide derived from a propeptide released in blood, is able to block the TREK-1 (KCNK2 or K2P2.1) channel activity. Spadin binds specifically to TREK-1 with an affinity of 10 nM. Spadin is an efficient antidepressant in mice[1].
DCPIB is a selective, reversible and potent inhibitor of volume-regulated anion channels (VRAC), voltage-dependently activates potassium channels TREK1 and TRAAK, inhibits TRESK, TASK1 and TASK3 (IC50s, 0.14, 0.95, 50.72 μM, respectively)[1]. DCPIB is also a selective blocker of swelling-induced chloride current (ICl,swell), with an IC50 of 4.1 μM in CPAE cells[2].
Cibenzoline is a potent inhibitor of KATP channel with directly affecting the pore-forming Kir6.2 subunit rather than the SUR1 subunit. Cibenzoline is a class Ia antiarrhythmic drug. Cibenzoline has little anticholinergic activity. Cibenzoline markedly attenuate LVPG which has a close relationship with myocardial contractility decreasing. Cibenzoline has the potential for the research of hypertrophic obstructive cardiomyopathy[1][2].
AP14145 hydrochloride is a potent KCa2 (SK) channel negative allosteric modulator with an IC50 of 1.1 μM for KCa2.2 (SK2) and KCa2.3 (SK3) channels. AP14145 hydrochloride inhibition strongly depends on two amino acids, S508 and A533 in the channel. AP14145 hydrochloride prolonged atrial effective refractory period (AERP) in rats and demonstrates antiarrhythmic effects in a Vernakalant-resistant porcine model of atrial fibrillation (AF)[1][2].
KRN4884 is a K+ channel opener. In the presence of intracellular ATP (1 mM), KRN4884 (0.1-3 μM) activates KATP channels in a concentration-dependent manner (EC50=0.55 μM).