δ-Dendrotoxin is a K+ channel blocker that can be obtained from the venom of the black mamba snake. δ-Dendrotoxin can be used in the study of neurological diseases[1].
Scyllatoxin (Leiurotoxin I) is a peptide toxin, it can be isolated from the venom of the scorpion (Leiurus quinquestriatus hebraeus). Scyllatoxin is a blocker of small-conductance KCa (SK) channel. Scyllatoxin enhances both norepinephrine (NE) and epinephrine (Epi) release in vivo[1].
ML402 is a selective TREK-1 activator.
ProTx-I, a venom toxin of the tarantula Thrixopelma pruriens, is a potent, selective CaV3.1 channel blocker with IC50 values of 0.2 μM and 31.8 μM for hCaV3.1 and hCaV3.2 respectively. ProTx-I is also a potent blocker for voltage-gated Na+ channels and inhibits KV 2.1 channels[1][2].
NS6180 is a novel potent and selective KCa3.1 channel inhibitor(IC50= 9 nM) prevents T-cell activation and inflammation.IC50 value: 9 nM [1]Target: KCa3.1 channel inhibitorin vitro: NS6180 inhibited cloned human KCa3.1 channels (IC50 = 9 nM) via T250 and V275, the same amino acid residues conferring sensitivity to triarylmethanes such as like TRAM-34. NS6180 inhibited endogenously expressed KCa3.1 channels in human, mouse and rat erythrocytes, with similar potencies (15–20 nM). NS6180 suppressed rat and mouse splenocyte proliferation at submicrolar concentrations and potently inhibited IL-2 and IFN-γ production, while exerting smaller effects on IL-4 and TNF-α and no effect on IL-17 production [1].in vivo: DNBS challenged rats were treated with two doses (3 and 10 mg·kg-1 b.i.d.) of NS6180 for 7 days in direct comparison with the IBD drug sulfasalazine (300 mg·kg-1 q.d.). Both doses of NS6180 significantly improved weight gain and decreased inflammation induced swelling of the colon as determined by relative colon weight [1].
Branaplam (LMI070; NVS-SM1) hydrochloride is a highly potent, selective and orally active survival motor neuron-2 (SMN2) splicing modulator with an EC50 of 20 nM for SMN. Branaplam hydrochloride inhibits human-ether-a-go-go-related gene (hERG) with an IC50 of 6.3 μM. Branaplam hydrochloride elevates full-length SMN protein and extends survival in a severe spinal muscular atrophy (SMA) mouse model[1][2].
Kv3 modulator 4 is a Kv3.1 (pEC50=5.45) and Kv3.2 modulator extracted from patent WO2018020263A1, Cyclobutyl structure[1].
DCEBIO, a derivative of 1-EBIO, is an extremely potent activator of Cl－ secretion in T84 colonic cells[1]. DCEBIO stimulates Cl－ secretion via the activation of hIK1 K＋ channels and the activation of an apical membrane Cl－ conductance[2].
Clamikalant sodium (HMR 1098) is an ATP-sensitive potassium (KATP) channel blocker. Clamikalant sodium can be used for the research of arrhythmia[1].
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.
Amifampridine (3,4-Diaminopyridine) phosphate is an orally active potassium channel blocker (PCB), can block presynaptic potassium channels[1]. Amifampridine phosphate can be used in Lambert-Eaton myasthenic syndrome (LEMS) research[1].
N-Bromoacetamide can irreversibly remove sodium channel inactivation in the cytoplasmic face of the membrane, also decreasing K current rapid inactivation[1][2].
GAL-021 sulfate is a potent BKCa-channel blocker. GAL-021 sulfate inhibits KCa1.1 in GH3 cells. GAL-021 sulfate is a novel breathing control modulator that is based on selective modification of the almitrine pharmacophore. GAL-021 sulfate increases minute ventilation in rats and non-human primates[1][2].
Flufenamic acid is a non-steroidal anti-inflammatory agent, inhibits cyclooxygenase (COX), activates AMPK, and also modulates ion channels, blocking chloride channels and L-type Ca2+ channels, modulating non-selective cation channels (NSC), activating K+ channels.
HsTX1, from the scorpion Heterometrus spinnifer, is a 34-residue, C-terminally amidated peptide cross-linked by four disulfide bridges. HsTX1, an the inhibitor of potassium channel, with IC50 for Kv1.3 of 12 pM inhibits TEM cell activation and attenuates inflammation in autoimmunity[1][2][3].
BDS-I known as blood depressing substance, is a marine toxin which can be extracted from Anemonia sulcata. BDS-I is a specific inhibitor of Potassium Channel, targeting to Kv3.4. BDS-I inhibits Aβ1-42-induced enhancement of KV3.4 activity, caspase-3 activation, and abnormal nuclear morphology of NGF-differentiated PC-12 cells. BDS-I reverts the Aβ peptide-induced cell death[1].
VU 0240551 is a small molecule inhibitor of the neuronal K-Cl cotransporter, KCC2 (IC50 = 560 nM for K+ uptake assay in KCC2-overexpressing cells).IC50 value: 560 nM [1]Target: K-Cl cotransporter(KCC2)VU 0240551 exhibits selectivity over the Na-K-2Cl cotransporter, NKCCl. VU 0240551 also inhibits hERG and L-type Ca2+ channels [1]. Herein we report the discovery and SAR of an improved novel antagonist (VU0463271) of the neuronal-specific potassium-chloride cotransporter 2 (KCC2), with an IC(50) of 61 nM and >100-fold selectivity versus the closely related Na-K-2Cl cotransporter 1 (NKCC1) and no activity in a larger panel of GPCRs, ion channels and transporters [2].
Glisoxepid-d4 is the deuterium labeled Glisoxepide. Glisoxepide, a sulphonamide derivative, is an orally available nonselective K(ATP) channel blocker, with antihyperglycemic activity and cardiovascular regulation effect[1][2][3].
Iptakalim hydrochloride, a lipophilic para-amino compound, is a novel ATP-sensitive potassium channel (KATP) opener, as well as an α4β2-containing nicotinic acetylcholine receptor (nAChR) antagonist[1].
Azimilide(NE-10064) is a class III antiarrhythmic compound, inhibits I(Ks) and I(Kr) in guinea-pig cardiac myocytes and I(Ks) (minK) channels expressed in Xenopus oocytes.IC50 value:Target: in vitro: Azimilide blocked HERG channels at 0.1 and 1 Hz with IC50s of 1.4 microM and 5.2 microM respectively. Azimilide blockade of HERG channels expressed in Xenopus oocytes and I(Kr) in mouse AT-1 cells was decreased under conditions of high [K+]e, whereas block of slowly activating I(Ks) channels was not affected by changes in [K+]e [1]. Azimilide suppressed the following currents (Kd in parenthesis): IKr (< 1 microM at -20 mV), IKs (1.8 microM at +30 mV), L-type Ca current (17.8 microM at +10 mV), and Na current (19 microM at -40 mV). Azimilide was a weak blocker of the transient outward and inward rectifier currents (Kd > or = 50 microM at +50 and -140 mV, respectively). Azimilide blocked IKr, IKs, and INa in a use-dependent manner. Furthermore, azimilide reduced a slowly inactivating component of Na current that might be important for maintaining the action potential plateau in canine ventricular myocytes [2]. In guinea pig ventricular myocytes, NE-10064 (0.3-3 microM) significantly prolonged action potential duration (APD) at 1 Hz. At 3 Hz, NE-10064 (0.3-1 microM) increased APD only slightly, and at 10 microM decreased APD and the plateau potential. NE-10064 potently blocked the rapidly activating component of the delayed rectifier, IKr (IC50 0.4 microM), and inhibited IKs (IC50 3 microM) with nearly 10-fold less potency [3].in vivo: NE-10064 (10 mg/kg intravenously, i.v.) reduced (p < 0.05) the incidence (8 of 12) of PES-induced ventricular tachycardia (VT). The cycle length of induced VT was not prolonged by NE-10064 (0.245 +/- 0.046 s predrug vs. 0.301 +/- 0.060 s postdrug). NE-10064 increased ventricular effective refractory period (VERP 166 +/- 5 ms predrug vs. 194 +/- 13 ms postdrug, p = 0.013), prolonged QTc interval (310 +/- 12 ms predrug vs. 350 +/- 16 ms postdrug, p = 0.004) and prolonged the effective refractory period (ERP) of noninfarcted myocardium (p = 0.045) [4].
Paederosidic acid methyl ester is a ATP‐sensitive K+ channel activator, isolated from P. scandens. Paederosidic acid methyl ester exhibits significant central analgesic activity, and enhances the threshold of pain by activating ATP‐sensitive K+ channel in the brain and spinal cord level[1].
Heteropodatoxin-2, a peptides of 30-amino acid, is a heteropodatoxin. Heteropodatoxin-2 blocks Kv4.2 current expressed in Xenopus laevis oocytes in a voltage-dependent manner, with less block at more positive potentials[1].
Tolbutamide is a first generation potassium channel blocker, sulfonylurea oral hypoglycemic drug.Target: Potassium ChannelTolbutamide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). Tolbutamide act by stimulating β cells of the pancreas to release insulin. Sulfonylureas increase both basal insulin secretion and meal-stimulated insulin release. Tolbutamide belongs to a class of medications called sulfonylureas. Tolbutamide inhibits both the basal and the cyclic AMP-stimulated protein kinase activities and the IC50 of Tolbutamide is 4 mM. Similar Tolbutamide concentrations are required for half maximal inhibition of in vitro lipolysis induced by hormones (norepinephrine and ACTH) or by dibutyryl cyclic AMP plus theophylline. Tolbutamide also inhibits both soluble and membrane-bound protein kinase from canine heart. The Tolbutamide inhibition of adipose tissue cyclic AMP-dependent protein kinase is one possible explanation for the antilipolytic effects of this drug [1]. Tolbutamide inhibits C6-glioma cell proliferation by increasing Cx43, which correlates with a reduction in pRb phosphorylation due to the up-regulation of the Cdk inhibitors p21 and p27 [2].
Immuno modulator-1 (compound 22) inhibits TNFα and IL-2 secretion in human peripheral blood mononuclear cells (hPBMC), with IC50 values of 4.7 and 26 nM, respectively. Immuno modulator-1 shows hERG potassium channel blocking effect, with Inhibitory percentage of 20% at 3 μM[1].
(R)-SKF 38393 ((±)-SKF-38393) hydrochloride is a potent and selective D1 dopamine receptor antagonist. (R)-SKF 38393 hydrochloride inhibits G protein-coupled inwardly rectifying potassium (GIRK) channel[1].
Cromakalim is a potassium channel opener. Cromakalim can be used as a bronchodilator in asthma. Cromakalim inhibits the spontaneous tone of human isolated bronchi in a concentration-related manner being nearly as effective as isoprenaline or theophylline[1].
(3R,5R)-Rosuvastatin is the (3R,5R)-enantiomer of Rosuvastatin. Rosuvastatin is a competitive HMG-CoA reductase inhibitor with an IC50 of 11 nM[1]. Rosuvastatin potently blocks human ether-a-go-go related gene (hERG) current with an IC50 of 195 nM[2]. Rosuvastatin reduces the expression of the mature hERG and the interaction of heat shock protein 70 (Hsp70) with the hERG protein. Rosuvastatin is very effective in lowering low-density lipoprotein (LDL) cholesterol, triglycerides, and C-reactive protein levels[3].
VU041 is a first submicromolar-affinity inhibitor of Anopheles (An.) gambiae and Aedes (Ae.) aegypti inward rectifier potassium 1 (Kir1) channels with IC50 values of 2.5 μM and 1.7 μM, respectively. VU041 inhibits appreciably is mammalian Kir2.1 (IC50 of 12.7 μM), and has less inhibitory effect on mammalian Kir1.1, Kir4.1, Kir6.2/SUR1, and Kir7.1. VU041 also induces impaired Malpighian tubule function[1].
Isopropyl unoprostone (Unoprostone isopropyl ester), an analogue of a prostaglandin metabolite, is a potent large conductance Ca2+-activated K+ (BK) channels activator. Isopropyl unoprostone has antiglaucoma effects, lowering intraocular pressure (IOP) by increasing aqueous humour outflow. Isopropyl unoprostone can improve retinal sensitivity and the protection of central retinal sensitivity[1][2].