VU0134992 hydrochloride

• CAT Number: I016422
• CAS Number: 1052515-91-9
• Molecular Formula: C20H32BrClN2O2
• Molecular Weight: 447.84
• Purity: ≥95%
• Synonyms: 2-(2-bromo-4-propan-2-ylphenoxy)-N-(2,2,6,6-tetramethylpiperidin-4-yl)acetamide;hydrochloride
• InChI: InChI=1S/C20H31BrN2O2.ClH/c1-13(2)14-7-8-17(16(21)9-14)25-12-18(24)22-15-10-19(3,4)23-20(5,6)11-15;/h7-9,13,15,23H,10-12H2,1-6H3,(H,22,24);1H
• InChIKey: QXKQUPCNSXWIDX-UHFFFAOYSA-N
• SMILES: CC(C)C1=CC(=C(C=C1)OCC(=O)NC2CC(NC(C2)(C)C)(C)C)Br.Cl

VU0134992 hydrochloride is the first subtype-preferring, orally active and selective Kir4.1 potassium channel pore blocker, with an IC50 of 0.97 µM. VU0134992 hydrochloride is 9-fold selective for homomeric Kir4.1 over Kir4.1/5.1 concatemeric channels (IC50=9 µM) at -120 mV[1].
VU0134992 hydrochloride 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[1].
The selectivity of VU0134992 hydrochloride for Kir4.1 versus nine other members of the Kir channel family was evaluated at concentrations ranging from 0.3 nM to 30 µM in 11-point CRC experiments, using established Tl+ flux assays. VU0134992 hydrochloride inhibits Kir3.1/Kir3.2 (92% inhibition at 30 µM, IC50=2.5 µM), Kir3.1/Kir3.4 (92% inhibition at 30 µM, IC50=3.1 µM), and Kir4.2 (100% inhibition at 30 µM, IC50=8.1 µM) with approximately the same efficacy and potency that VU0134992 inhibits Kir4.1 (100% at 30 µM, IC50=5.2 µM)[1].
VU0134992 hydrochloride (50-100 mg/kg; oral gavage) statistically significantly increased urinary Na+ as well as K+ excretion[1].

Reference

[1]. Kharade SV, et al. Discovery, Characterization, and Effects on Renal Fluid and Electrolyte Excretion of the Kir4.1 Potassium Channel Pore Blocker, VU0134992. Mol Pharmacol. 2018 Aug;94(2):926-937.
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