| Name | VU0134992 hydrochloride |
| Description | VU0134992 hydrochloride is the first subtype-preferring, orally active and selective blocker of the Kir4.1 potassium channel pore (IC50: 0.97 μM). |
| Animal Research | VU0134992 hydrochloride (250-300 g Male Sprague-Dawley rats;50 and 100 mg/kg) Oral gavage |
| In vitro | In whole-cell patch-clamp electrophysiology experiments, VU0134992 inhibits Kir4.1 with an IC50 value of 0.97 M and is 9-fold selective for homomeric Kir4.1 over Kir4.1/5.1 concatemeric channels (IC50 = 9 M) at -120 mV. In thallium (Tl+) flux assays, VU0134992 is greater than 30-fold selective for Kir4.1 over Kir1.1, Kir2.1, and Kir2.2; is weakly active toward Kir2.3, Kir6.2/SUR1, and Kir7.1; and is equally active toward Kir3.1/3.2, Kir3.1/3.4, and Kir4.2. This potency and selectivity profile is superior to Kir4.1 inhibitors amitriptyline, nortriptyline, and fluoxetine. Medicinal chemistry identified components of VU0134992 that are critical for inhibiting Kir4.1. Patch-clamp electrophysiology, molecular modeling, and site-directed mutagenesis identified pore-lining glutamate 158 and isoleucine 159 as critical residues for block of the channel. |
| In vivo | VU0134992 displayed a large free unbound fraction (fu) in rat plasma (fu = 0.213).Consistent with the known role of Kir4.1 in renal function, oral dosing of VU0134992 led to a dose-dependent diuresis, natriuresis, and kaliuresis in rats.Thus, VU0134992 represents the first in vivo active tool compound for probing the therapeutic potential of Kir4.1 as a novel diuretic target for the treatment of hypertension. |
| Storage | Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | DMSO : 230 mg/mL (513.58 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 5 mg/mL (11.16 mM), Sonication is recommended.
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| Keywords | whole-cell | VU-0134992 hydrochloride | VU0134992 Hydrochloride | VU-0134992 | VU0134992 | VU 0134992 Hydrochloride | VU 0134992 | selective | PotassiumChannel | Potassium Channel | patch-clamp | oral | natriuresis | Kir4.1 | KcsA | kaliuresis | Inhibitor | inhibit | hypertension | electrophysiology | diuresis |
| Inhibitors Related | Minoxidil sulfate | Tannic acid | Hydrochlorothiazide | 1,8-Cineole | Tetraethylammonium bromide | Ursodeoxycholic acid | Chenodeoxycholic acid | Minoxidil | Chlorzoxazone | 2,2,2-Trichloroethanol | Taurocholic acid sodium salt hydrate | Indapamide |
| Related Compound Libraries | Pain-Related Compound Library | Bioactive Compound Library | Membrane Protein-targeted Compound Library | Inhibitor Library | NO PAINS Compound Library | Orally Active Compound Library | Bioactive Compounds Library Max | Potassium Channel Targeted Library | Ion Channel Targeted Library | Anti-Cancer Compound Library |
United States
