Mitiglinide Calcium (formerly KAD-1229; S-21403; KAD1229; S21403; Glufast), the calcium salt of Mitiglinide, is a potassiun channel blocker that has been approved as a blood glucose-lowering drug for the treatment of type 2 diabetes. It acts by stimulating insulin secretion by closing the ATP-sensitive K+ channels in pancreatic beta-cells.

Physicochemical Properties

Molecular Formula	(C19H24NO3)2.CA
Molecular Weight	668.88
Exact Mass	668.313
CAS #	145525-41-3
Related CAS #	Mitiglinide calcium hydrate;207844-01-7;Mitiglinide;145375-43-5
PubChem CID	5478927
Appearance	White to off-white solid powder
Density	1.175
Boiling Point	519.6ºC at 760 mmHg
Melting Point	146-148ºC
Flash Point	268ºC
Vapour Pressure	1.27E-11mmHg at 25°C
LogP	5.594
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	8
Heavy Atom Count	47
Complexity	411
Defined Atom Stereocenter Count	6
SMILES	C1CC[C@H]2CN(C[C@H]2C1)C(=O)C[C@H](CC3=CC=CC=C3)C(=O)[O-].C1CC[C@H]2CN(C[C@H]2C1)C(=O)C[C@H](CC3=CC=CC=C3)C(=O)[O-].[Ca+2]
InChi Key	PMRVFZXOCRHXFE-FMEJWYFOSA-L
InChi Code	InChI=1S/2C19H25NO3.Ca/c2*21-18(20-12-15-8-4-5-9-16(15)13-20)11-17(19(22)23)10-14-6-2-1-3-7-14;/h2*1-3,6-7,15-17H,4-5,8-13H2,(H,22,23);/q;;+2/p-2/t2*15-,16+,17-;/m00./s1
Chemical Name	calcium;(2S)-4-[(3aS,7aR)-1,3,3a,4,5,6,7,7a-octahydroisoindol-2-yl]-2-benzyl-4-oxobutanoate
Synonyms	KAD-1229;S 21403;KAD 1229; S21403;KAD1229; S-21403; Mitiglinide calcium; Glufast.
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

Targets	ATP-sensitive potassium (KATP) channels on pancreatic β-cells [1]
ln Vitro	Mitiglinide Calcium reduces the Kir6.2/SUR1 channel currents in a dose-dependent manner (IC50 value, 100 nM) but does not significantly inhibit either Kir6.2/SUR2A or Kir6.2/SUR2B channel currents even at high doses (more than 10 μM) in COS-1 cells[1]. In isolated rat pancreatic islets and MIN6 pancreatic β-cells, Mitiglinide Calcium (KAD-1229) (1-1000 nM) dose-dependently stimulated insulin secretion, with a more potent effect under high glucose conditions. At 100 nM, it increased insulin release by 110% under high glucose (16.7 mM) and by 45% under low glucose (5.6 mM) in rat islets. Compared to sulfonylureas (glibenclamide) and nateglinide, it exhibited a faster onset and shorter duration of insulin-stimulating effect, with reversible blockade of KATP channels[1] - In patch-clamp recordings of MIN6 cells, Mitiglinide Calcium (KAD-1229) (10-1000 nM) dose-dependently blocked KATP currents. At 300 nM, it inhibited KATP currents by 78%, leading to membrane depolarization and subsequent Ca²⁺ influx, which triggered insulin granule exocytosis[1]
ln Vivo	Up to five hours after a meal load, mitiglinide calcium (1-3 mg/kg; po) inhibits both the rise in plasma glucose levels observed following the meal load and the area under the curve for plasma glucose levels (AUCglucose). In STZ-induced type 2 diabetic rats, oral administration of Mitiglinide Calcium (KAD-1229) (0.3 mg/kg, 1 mg/kg, 3 mg/kg) 30 minutes before a meal dose-dependently reduced postprandial plasma glucose levels. The 3 mg/kg dose decreased the peak postprandial glucose concentration by 42% and the area under the glucose curve (AUC) by 38% compared to the control group. It also increased postprandial plasma insulin concentrations by 65% at 1 mg/kg, with a faster onset of hypoglycemic effect (within 30 minutes) and shorter duration (≤4 hours) than glibenclamide[2]
Enzyme Assay	KATP channel activity assay: MIN6 cells were seeded on glass coverslips and cultured for 24-48 hours. Whole-cell patch-clamp recordings were performed to measure KATP currents. Mitiglinide Calcium (KAD-1229) was applied to the extracellular solution at gradient concentrations (10-1000 nM). The voltage protocol included a holding potential of -70 mV, depolarizing steps to +40 mV (500 ms), and repolarization to -70 mV. Peak KATP current amplitude was normalized to the control to calculate the blocking rate[1]
Cell Assay	Pancreatic β-cell insulin secretion assay: Rat pancreatic islets were isolated and cultured in RPMI 1640 medium. MIN6 cells were seeded in 24-well plates (5×10⁴ cells/well). Mitiglinide Calcium (KAD-1229) (1 nM, 10 nM, 100 nM, 1000 nM) was added to medium with low (5.6 mM) or high (16.7 mM) glucose, and cells were incubated for 2 hours. Insulin concentration in the supernatant was measured by radioimmunoassay, and the effect was compared with glibenclamide and nateglinide[1]
Animal Protocol	Animal/Disease Models: Pregnant Wistar rats (12 weeks)[2] Doses: 0.3 mg/kg, 1 mg/kg, 3 mg/kg Route of Administration: Oral administration Experimental Results: Dose-dependently suppressed AUCglucose levels. STZ-induced type 2 diabetic rat model: Male Wistar rats were injected with STZ (30 mg/kg, intraperitoneal) to establish the type 2 diabetic model. Rats with fasting blood glucose ≥11.1 mmol/L were selected and randomly divided into control and treatment groups. Mitiglinide Calcium (KAD-1229) was suspended in 0.5% carboxymethylcellulose sodium (CMC-Na) and administered orally at 0.3 mg/kg, 1 mg/kg, or 3 mg/kg 30 minutes before a standard meal. Postprandial plasma glucose and insulin concentrations were measured at 0, 30, 60, 120, and 240 minutes after the meal[2]
References	[1]. The effects of mitiglinide (KAD-1229), a new anti-diabetic drug, on ATP-sensitive K+ channels and insulin secretion: comparison with the sulfonylureas and nateglinide. Eur J Pharmacol. 2001 Nov 9;431(1):119-25. [2]. Effect of KAD-1229, a novel hypoglycaemic agent, on plasma glucose levels after meal load in type 2 diabetic rats. Clin Exp Pharmacol Physiol. May-Jun 2002;29(5-6):423-7.
Additional Infomation	Kad 1229 is a polymer. Mitiglinide Calcium (KAD-1229) is a meglitinide analog antidiabetic drug developed for the treatment of type 2 diabetes mellitus[1][2] - Its core hypoglycemic mechanism involves rapid and reversible blockade of KATP channels on pancreatic β-cells, promoting glucose-dependent insulin secretion[1] - Compared to sulfonylureas (e.g., glibenclamide), it has a faster onset (30 minutes) and shorter duration of action (≤4 hours), making it suitable for controlling postprandial hyperglycemia[1][2] - In vitro studies show it has a more glucose-dependent insulin-stimulating effect than nateglinide, reducing the risk of hypoglycemia under low glucose conditions[1]

Solubility Data

Solubility (In Vitro)

DMSO:<1 mg/mL Water:<1 mg/mL Ethanol: 2 mg/mL (2.99 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 0.5 mg/mL (1.50 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 5.0 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: ≥ 0.5 mg/mL (1.50 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 5.0 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: ≥ 0.5 mg/mL (1.50 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 5.0 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	1.4950 mL	7.4752 mL	14.9504 mL
	5 mM	0.2990 mL	1.4950 mL	2.9901 mL
	10 mM	0.1495 mL	0.7475 mL	1.4950 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.