Gliquidone (also known as AR-DF 26; Glurenorm; Beglynor) is a potent ATP-sensitive K+ channel antagonist with potential anti0diabetic activity. It inhibits ATP-sensitive K + channel with an IC50 of 27.2 NM. As a sulfonylurea anti-diabetic drug , it is used in the treatment of diabetes mellitus type 2. In patients with type 2 diabetes mellitus, gliquidone reduced the mean plasma glucose levels by 15% and increased insulin levels by 40%. In Caucasian patients with new-onset diabetes mellitus (NODM) after kidney transplantation, gliquidone reduced fasting blood glucose (FBG) from 154 mg/dl to 120 mg/dl.

Physicochemical Properties

Molecular Formula	C27H33N3O6S
Molecular Weight	527.63
Exact Mass	527.208
CAS #	33342-05-1
Related CAS #	Gliquidone-d6
PubChem CID	91610
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Melting Point	179ºC
Index of Refraction	1.624
LogP	3.11
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	7
Heavy Atom Count	37
Complexity	948
Defined Atom Stereocenter Count	0
SMILES	O=S(C1=CC=C(CCN(C(C(C)(C)C2=C3C=C(OC)C=C2)=O)C3=O)C=C1)(NC(NC4CCCCC4)=O)=O
InChi Key	LLJFMFZYVVLQKT-UHFFFAOYSA-N
InChi Code	InChI=1S/C27H33N3O6S/c1-27(2)23-14-11-20(36-3)17-22(23)24(31)30(25(27)32)16-15-18-9-12-21(13-10-18)37(34,35)29-26(33)28-19-7-5-4-6-8-19/h9-14,17,19H,4-8,15-16H2,1-3H3,(H2,28,29,33)
Chemical Name	1-cyclohexyl-3-[4-[2-(7-methoxy-4,4-dimethyl-1,3-dioxoisoquinolin-2-yl)ethyl]phenyl]sulfonylurea
Synonyms	Gliquidone; Glurenorm; Beglynor; Glikvidon; Glycvidon; Sanofi Synthelabo brand of gliquidone; Yamanouchi brand of gliquidone; AR-DF 26
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
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	In vitro activity: Gliquidone is an ATP-sensitive K+ channel antagonist. In mice, gliquidone (10 or 40 μg) antagonized morphine (20 mg/kg) induced hypermotility in a dose-dependent way. These results suggested that ATP-sensitive K+ channels played an important role in morphine-induced hypermotility.
ln Vivo	Gliquidone (0.1–1.0 μg per mouse i.c.v.) prevents antinociception produced by amitriptyline and clomipramine in a dose-dependent manner in male swiss albino mice. Gliquidone (0.06–16 μg per mouse, i.c.v.) antagonizes the antinociception induced by buprenorphine, morphine and methadone. Gliquidone (6 μg per mouse, i.c.v.) prevents the antinociception induced by clonidine (0.125 mg/kg, s.c.) and guanabenz (0.30 mg/kg, s.c.), while a lower dose of gliquidone (3 μg per mouse, i.c.v.) is ineffective. Glurenorm (10 mg/kg) given to the diabetic rats produces significant reductions in blood glucose, nonenzymatic glycosylation, and total protein in the lenses, and significantly increases in glutathione levels in the lenses.
Animal Protocol	10 mg/kg Mice
ADME/Pharmacokinetics	Biological Half-Life The mean terminal half-life was approximately 8 hours (range 5.7-9.4 hours)
References	Fundam Clin Pharmacol.1991;5(2):107-15;Arzneimittelforschung.1997 Mar;47(3):247-52.
Additional Infomation	1-cyclohexyl-3-[4-[2-(7-methoxy-4,4-dimethyl-1,3-dioxo-2-isoquinolinyl)ethyl]phenyl]sulfonylurea is a member of isoquinolines. Gliquidone is a sulfonylurea drug used to treat diabetes mellitus type 2. It is an ATP-dependent K+ (KATP) channel blocker. This block causes a depolarization which leads to activation of voltage-dependent Ca channels and Ca2+ influx, and eventually increases insulin release. Gliquidone is a potent, second-generation sulfonylurea with antihyperglycemic activity. Like other second-generation compounds, gliquidone exerts greater binding affinity to SUR1 and increased potency compared to first-generation compounds. In addition, this agent exerts peroxisome proliferator-activated receptor (PPAR) gamma agonistic activity. Drug Indication Used in the treatment of diabetes mellitus type 2. Mechanism of Action The mechanism of action of gliquidone in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells, and increasing sensitivity of peripheral tissues to insulin. Gliquidone likely binds to ATP-sensitive potassium channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Membrane depolarization stimulates calcium ion influx through voltage-sensitive calcium channels. This increase in intracellular calcium ion concentration induces the secretion of insulin. Pharmacodynamics Gliquidone is an anti-diabetic drug in the sulfonylurea class. In patients with diabetes mellitus, there is a deficiency or absence of a hormone manufactured by the pancreas called insulin. Insulin is the main hormone responsible for the control of sugar in the blood. Gliquidone is an antidiabetic medication which is used in those patients with adult maturity onset or non-insulin dependent diabetes (NIDDM). It works by lowering blood sugar levels by stimulating the production and release of insulin from the pancreas. It also promotes the movement of sugar from the blood into the cells in the body which need it.

Solubility Data

Solubility (In Vitro)

DMSO:105 mg/mL (199.0 mM) Water:<1 mg/mL Ethanol:6 mg/mL (11.4 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.74 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), suspension solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: 2.5 mg/mL (4.74 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (4.74 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.. Solubility in Formulation 4: 2% DMSO +Corn oil : 5mg/mL  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.8953 mL	9.4763 mL	18.9527 mL
	5 mM	0.3791 mL	1.8953 mL	3.7905 mL
	10 mM	0.1895 mL	0.9476 mL	1.8953 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.