VU0134992 hydrochloride

SKU: orb1308951

Description

VU0134992 hydrochloride

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 1052515-91-9
• MW: 447.84
• Purity: 100.00%
• Formula: C₂₀H₃₂BrClN₂O₂
• SMILES: Cl.CC(C)c1ccc(OCC(=O)NC2CC(C)(C)NC(C)(C)C2)c(Br)c1
• Target: Potassium Channel
• Solubility: DMSO:230 mg/mL (513.58 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:5 mg/mL (11.16 mM)

Bioactivity

• 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.
• 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.
• Animal Research:
  VU0134992 hydrochloride (250-300 g Male Sprague-Dawley rats;50 and 100 mg/kg) Oral gavage

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

diuresis, natriuresis, patch-clamp, oral, kaliuresis, inhibit, KcsA, Kir4.1, hypertension, electrophysiology, Inhibitor, whole-cell, PotassiumChannel, Potassium Channel, selective, VU 0134992, VU 0134992 Hydrochloride, VU0134992, VU-0134992, VU0134992 Hydrochloride, VU0134992 hydrochloride, VU-0134992 hydrochloride, VU-0134992 Hydrochloride

Compound Identifiers

PubChem CID

2943675