Mitiglinide (also known as KAD-1229; S21403) is a Potassiun Channel blocker that is used as a blood glucose-lowering drug, it stimulates insulin secretion by closing the ATP-sensitive K+ channels in pancreatic beta-cells. Mitiglinide is thought to stimulate insulin secretion by closing the ATP-sensitive K(+) K(ATP) channels in pancreatic beta-cells. Mitiglinide may be potential useful for the treatment of type 2 diabetes.

Physicochemical Properties

Molecular Formula	C19H24NO3
Molecular Weight	315.41
Exact Mass	315.183
CAS #	145375-43-5
Related CAS #	Mitiglinide calcium;145525-41-3;Mitiglinide calcium hydrate;207844-01-7;Mitiglinide-d8 calcium hydrate;(2R)-Mitiglinide-d5 calcium;Mitiglinide-d5 calcium
PubChem CID	121891
Appearance	Typically exists as solid at room temperature
Density	1.2±0.1 g/cm3
Boiling Point	519.6±43.0 °C at 760 mmHg
Flash Point	268.0±28.2 °C
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.567
LogP	4.73
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	5
Heavy Atom Count	23
Complexity	416
Defined Atom Stereocenter Count	3
SMILES	OC(C(CC(N1CC2CCCCC2C1)=O)CC1C=CC=CC=1)=O
InChi Key	WPGGHFDDFPHPOB-BBWFWOEESA-N
InChi Code	InChI=1S/C19H25NO3/c21-18(20-12-15-8-4-5-9-16(15)13-20)11-17(19(22)23)10-14-6-2-1-3-7-14/h1-3,6-7,15-17H,4-5,8-13H2,(H,22,23)/t15-,16+,17-/m0/s1
Chemical Name	(2S)-4-[(3aS,7aR)-1,3,3a,4,5,6,7,7a-octahydroisoindol-2-yl]-2-benzyl-4-oxobutanoic acid
Synonyms	KAD-1229;KAD 1229; KAD1229; S 21403; Mitiglinide; 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
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 COS-1 cells, mitigamininde reduces the Kir6.2/SUR1 channel currents in a dose-dependent manner (IC50 of 100 nM), but even at high concentrations (more than 10 μM), it does not significantly inhibit the Kir6.2/SUR2A or Kir6.2/SUR2B channel currents[1].
ln Vivo	Up to five hours after a meal load, mitiglinide (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).
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.
References	[1]. Y Sunaga, et al. 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]. Kiyoshi Ichikawa, et al. 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	Mitiglinide is a monocarboxylic acid and a member of benzenes. Mitiglinide is a drug for the treatment of type 2 diabetes. It may stimulate insulin secretion in beta-cells by closing off ATP dependant potassium ion channels. Mitiglinide is a succinic acid derivative with hypoglycemic activity. Like other meglitinide-type compounds, mitiglinide has a high affinity for SUR1 subunits. Drug Indication For the treatment of type 2 diabetes. Mechanism of Action Mitiglinide is thought to stimulate insulin secretion by binding to and blocking ATP-sensitive K(+) (K(ATP)) channels (Kir6.2/SUR1 complex, KATP channels) in pancreatic beta-cells. Closure of potassium channels causes depolarization which stimulates calcium influx through voltage-gated calcium channels. High intracellular calcium subsequently triggers the exocytosis of insulin granules. Pharmacodynamics Mitiglinide belongs to the meglitinide class of blood glucose-lowering drugs. It is approved for use in Japan but has not yet gained FDA approval.

Solubility Data

Solubility (In Vitro)

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

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.1705 mL	15.8524 mL	31.7048 mL
	5 mM	0.6341 mL	3.1705 mL	6.3410 mL
	10 mM	0.3170 mL	1.5852 mL	3.1705 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.