VU0134992 HCl is the first isoform-preferred, orally bioactive and selective blocker of the inwardly rectifying potassium channel Kir4.1 with IC50 of 0.97 μM. VU0134992 HCl is 9 times more selective for the Kir4.1 co-shared channel than the Kir4.1/5.1 co-shared channel (IC50=9 μM) at -120 mV.

Physicochemical Properties

Molecular Formula	C20H32BRCLN2O2
Molecular Weight	447.837284088135
Exact Mass	446.133
CAS #	1052515-91-9
Related CAS #	VU0134992;755002-90-5
PubChem CID	2943675
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	5
Heavy Atom Count	26
Complexity	449
Defined Atom Stereocenter Count	0
SMILES	BrC1C=C(C=CC=1OCC(NC1CC(C)(C)NC(C)(C)C1)=O)C(C)C.Cl
InChi Key	QXKQUPCNSXWIDX-UHFFFAOYSA-N
InChi Code	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
Chemical Name	2-(2-bromo-4-propan-2-ylphenoxy)-N-(2,2,6,6-tetramethylpiperidin-4-yl)acetamide;hydrochloride
Synonyms	VU-0134992 HCl; VU 0134992 HCl
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	VU0134992 hydrochloride has a selectivity for Kir4.1 that is more than thirty times more than that of Kir1.1, Kir2.1, and Kir2.2. Its activity is the same toward Kir3.1/3.2, Kir3.1/3.4, and Kir4.2, but it is weak against Kir2.3, Kir6.2/SUR1, and Kir7.1[1]. Using a well-established Tl+ flux assay, an 11-point CRC experiment was conducted to assess the selectivity of VU0134992 hydrochloride for Kir4.1 against nine other members of the Kir channel family spanning a dose range of 0.3 nM to 30 µM. The study reports that VU0134992 Hydrochloride exhibits the same level of efficacy and potency as VU0134992 when it comes to inhibiting 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).
ln Vivo	The oral gavage of VU0134992 hydrochloride (50-100 mg/kg) considerably increases the excretion of K+ and Na+ in the urine [1].
Animal Protocol	Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat (250-300 g) [1] Doses: po (oral gavage): 50 and 100 mg/kg Experimental Results: Urinary Na+ and K+ excretion increased Dramatically.
References	[1]. 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.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~558.24 mM) H2O : ~2.27 mg/mL (~5.07 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.64 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.64 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (4.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2329 mL	11.1647 mL	22.3294 mL
	5 mM	0.4466 mL	2.2329 mL	4.4659 mL
	10 mM	0.2233 mL	1.1165 mL	2.2329 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.