|S1658||Dofetilide||<1 mg/mL||88 mg/mL||<1 mg/mL|
|S2456||Chlorpromazine HCl||71 mg/mL||71 mg/mL||71 mg/mL|
|S1979||Amiodarone HCl||<1 mg/mL||23 mg/mL||11 mg/mL|
|S1344||Glimepiride||<1 mg/mL||11 mg/mL||<1 mg/mL|
|S1160||TRAM-34||<1 mg/mL||0.4 mg/mL||<1 mg/mL|
|S1426||Repaglinide||<1 mg/mL||91 mg/mL||91 mg/mL|
|S1971||Nicorandil||17 mg/mL||42 mg/mL||42 mg/mL|
|S2502||Quinine HCl Dihydrate||43 mg/mL||79 mg/mL||79 mg/mL|
|S1716||Glyburide (Glibenclamide)||<1 mg/mL||99 mg/mL||<1 mg/mL|
|S2443||Tolbutamide||<1 mg/mL||54 mg/mL||54 mg/mL|
|S3151||Gliquidone||<1 mg/mL||105 mg/mL||6 mg/mL|
|S2114||Dronedarone HCl||<1 mg/mL||80 mg/mL||40 mg/mL|
|S2489||Nateglinide||<1 mg/mL||63 mg/mL||63 mg/mL|
|S8016||Vonoprazan Fumarate (TAK-438)||<1 mg/mL||62 mg/mL||<1 mg/mL|
|S2825||ML133 HCl||<1 mg/mL||63 mg/mL||6 mg/mL|
|S2562||Hydralazine HCl||1 mg/mL||<1 mg/mL||<1 mg/mL|
|S2601||Gliclazide||<1 mg/mL||65 mg/mL||<1 mg/mL|
|S4037||Doxapram HCl||25 mg/mL||87 mg/mL||2 mg/mL|
|S4630||Diazoxide||<1 mg/mL||46 mg/mL||<1 mg/mL|
|S4733||Retigabine||<1 mg/mL||60 mg/mL||35 mg/mL|
|S4632||Hexachlorophene||<1 mg/mL||81 mg/mL||81 mg/mL|
|S4734||Retigabine 2HCl||75 mg/mL||75 mg/mL||25 mg/mL|
|S2073||Mitiglinide Calcium||<1 mg/mL||<1 mg/mL||2 mg/mL|
- Potassium Channel阻害剤(23)
Dofetilide is a selective potassium channel ((hERG)) blocker, used as a Class III antiarrhythmic drug.
Chlorpromazine HCl is a dopamine and potassium channel inhibitor with IC50 of 6.1 and 16 μM for inward-rectifying K+ currents and time-independent outward currents.
Low-micromolar amounts of chlorpromazine inhibit SARS-CoV-induced cytopathology. Vero E6 cells in 96-well plates were infected with SARS-CoV isolate Frankfurt-1 (MOI, 0.005) in the presence of 0 to 16 μM CPZ (B), given at t of +1 h p.i. Cells were incubated for 3 days, and viability was monitored using an MTS assay. In parallel, potential compound cytotoxicity was monitored in mock-infected Vero E6 cells. Graphs show the results (averages and SD) of a representative experiment that was performed in quadruplicate. All experiments were repeated at least twice. For each compound, the EC50, CC50, and SI values are given.
Amiodarone HCl is a sodium/potassium-ATPase inhibitor and an autophagy activator, used to treat various types of cardiac dysrhythmias.
Drugs across therapeutic indications induce lipid formation in hiPS-CM. Lipid accumulation was detected in cardiac cells using the LipidTox plate-based fluorescent assay on the Thermo Scientific CellInsight High Content platform. A) Ten drugs increased lipid levels in hiPS-CM following 48 h treatment. The lowest drug dose that induced a N1.5-fold increase in lipid formation is shown. B) Representative images (20×) from the assay are shown to the right. All drugs had >55% cell viability at 48 h at these tested concentrations. C) Of these 10 drugs, 8 significantly increased lipid accumulation following only 24 h treatment (images not shown). All drugs had >80% cell viability at 24 h at these drug doses. The graphs represent the mean fold-change of the lowest concentration of drug that significantly induced lipid formation >1.5-fold more than vehicle control. *P<0.05, **P<0.01, and ***P<0.0001.
Glimepiride is a potent Kir6.2/SUR inhibitor with IC50 of 3.0 nM, 5.4 nM, and 7.3 nM for SUR1, SUR2A and SUR2B, used in the treatment of type 2 diabetes mellitus.
(E) ELISA analysis for C-peptide levels in the presence of vehicle, diazoxide and glimepiride. (F) The fold change of C-peptide content after diazoxide and glimepiride stimulation. Diazoxide and glimepiride decreased and increased C-peptide secretion in wild-type and heterozygous mutated cells, respectively. Neither diazoxide nor glimepiride had an effect on homozygous mutated cells.
TRAM-34 is a selective and potent inhibitor of the intermediate-conductance Ca2+-activated K+ channel (IKCa1, KCa3.1) with Kd of 20 nM, 200- to 1500-fold selective over other ion channels, and does not block cytochrome P450.
Repaglinide is a potassium channel blocker, which lowers blood glucose by stimulating the release of insulin from the pancreas, used the treatment of type II diabetes.
Nicorandil is a potassium channel activator, and stimulates guanylate cyclase to increase formation of cyclic GMP (cGMP).
(G) The fold change of C-peptide content after octreotide, nicorandil and nifedipine treatment. Octreotide, nicorandil and nifedipine decreased insulin secretion in wild-type, heterozygous mutated and homozygous mutated cells.
Quinine HCl Dihydrate is a white crystalline K+ channel blocker, used to treat malaria.
Glyburide (Glibenclamide) is a known blocker of vascular ATP-sensitive K+ channels (KATP), used in the treatment of type 2 diabetes.
Tolbutamide is an inhibitor of potassium channel, used for type II diabetes.
Gliquidone is an ATP-sensitive K+ channel antagonist with IC50 of 27.2 nM.
Dronedarone HCl is a multichannel blocker targeting potassium channel, sodium channel and calcium channel, used as an antiarrhythmic drug for treatment of atrial fibrillation (AF).
Results of hit validation experiments for these four compounds for animals treated at L1 stage at four different concentrations (0.5, 5, 25, and 50 μM). The blue bars represent the values obtained from the original screen as reference points. Error bars are standard error of the mean. Statistical significance for all different doses for individual compounds was calculated with respect to the lowest concentration using two-tailed, t-test (nZ70 animals except n = 37 for Geld 25 μM). The statistical significance values are represented as P<0.05 (*) and P<0.005 (**).
Nateglinide is an insulin secretagog agent that lowers blood glucose levels by stimulating insulin secretion from the pancreas.
Vonoprazan Fumarate (TAK-438) is a novel P-CAB (potassium-competitive acid blocker) that reversibly inhibits H+/K+, ATPase with IC50 of 19 nM (pH 6.5), controls gastric acid secretion. Phase 3.
ML133 HCl is a selective potassium channel inhibitor for Kir2.1 with IC50 of 1.8 μM (pH 7.4) and 290 nM (pH 8.5), has no effect on Kir1.1 and weak activity for Kir4.1 and Kir7.1.
Hydralazine HCl is a hydrochloride salt of hydralazine, which is a direct-acting smooth muscle relaxant used to treat hypertension by acting as a vasodilator primarily in arteries and arterioles.
Gliclazide is a whole-cell beta-cell ATP-sensitive potassium currents blocker with an IC50 of 184 nM.
Doxapram HCl inhibits TASK-1, TASK-3, TASK-1/TASK-3 heterodimeric channel function with EC50 of 410 nM, 37 μM, 9 μM, respectively.
Diazoxide is a well-known small molecule that activates KATP channels in the smooth muscle of blood vessels and pancreatic beta-cells by increasing membrane permeability to potassium ions.
Retigabine(free base) is a novel anticonvulsant with activity in a broad range of seizure models. The mechanism of action involves opening of neuronal K(V)7.2-7.5 (formerly KCNQ2-5) voltage-activated K(+) channels.
Hexachlorophene is a potent KCNQ1/KCNE1 potassium channel activator with EC50 of 4.61 ± 1.29 μM; It can also attenuate Wnt/beta-catenin signaling through the Siah-1-mediated beta-catenin degradation.
Retigabine is a novel anticonvulsant with activity in a broad range of seizure models. The mechanism of action involves opening of neuronal K(V)7.2-7.5 (formerly KCNQ2-5) voltage-activated K(+) channels.
Mitiglinide Calcium is a blood glucose-lowering drugs, stimulating insulin secretion by closing the ATP-sensitive K+ channels in pancreatic beta-cells.