Powder: -20°C for 3 years | In solvent: -80°C for 1 year
VU0134992 hydrochloride is the first subtype-preferring, orally active and selective blocker of Kir4.1 potassium channel pore(IC50 : 0.97 μM).
Pack Size | Availability | Price/USD | Quantity |
---|---|---|---|
2 mg | In stock | $ 34.00 | |
5 mg | In stock | $ 55.00 | |
10 mg | In stock | $ 98.00 | |
25 mg | In stock | $ 183.00 | |
50 mg | In stock | $ 312.00 | |
100 mg | In stock | $ 531.00 | |
1 mL * 10 mM (in DMSO) | In stock | $ 61.00 |
Description | VU0134992 hydrochloride is the first subtype-preferring, orally active and selective blocker of Kir4.1 potassium channel pore(IC50 : 0.97 μM). |
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. |
Animal Research | VU0134992 hydrochloride (250-300 g Male Sprague-Dawley rats;50 and 100 mg/kg) Oral gavage |
Molecular Weight | 447.84 |
Formula | C20H32BrClN2O2 |
CAS No. | 1052515-91-9 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 230 mg/mL (513.58 mM), sonification is recommended.
You can also refer to dose conversion for different animals. More
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VU0134992 hydrochloride 1052515-91-9 Membrane transporter/Ion channel Potassium Channel VU0134992 oral hypertension patch-clamp electrophysiology Kir4.1 VU 0134992 Inhibitor natriuresis inhibit VU-0134992 hydrochloride whole-cell VU-0134992 Hydrochloride VU0134992 Hydrochloride selective kaliuresis VU 0134992 Hydrochloride KcsA VU-0134992 diuresis inhibitor