Vildagliptin

Orally administrated at a single dose

2-Pyrrolidinecarbonitrile, 1-[2-[(3-hydroxytricyclo[3.3.1.13, 7]dec-1-yl)amino]acetyl]-, (2S)-

Vildagliptin (LAF-237) inhibits DPP 4 with IC50 of 2.3 nM.

0.5% carboxymethylcellulose (CMC) and 0.2% Tween 80

Vildagliptin is the most stable DPP-IV inhibitor, binding in the S1- and S2-catalytic sites of DPP-IV, possessing a P-1 site transition-state mimetic. [1]

DPP-IV Inhibition Measurement, An extract from human colonic carcinoma cells (Caco-2) is used as the source of DPP-IV in the assay. The cells are differentiated to induce DPP-IV expression as described. Cell extract is prepared from cells solubilized in lysis buffer (10 mM Tris-HCl, 0.15 M NaCl, 0.04 T.I.U. (trypsin inhibitor unit) aprotinin, 0.5% nonidet-P40, pH 8.0) then centrifuged at 3.5x4g for 30 min at 4 C to remove cell debris. The assay is conducted by adding 20 ug of solubilized Caco-2 protein, diluted to a final volume of 125 uL in assay buffer (25 mM Tris-HCl pH 7.4, 140 mM NaCl, 10 mM KCl, 1% bovine serum albumin) to 96-well flat-bottom microtiter plates. The reaction is initiated by adding 25 uL of 1 mM substrate. The reaction is run at room temperature for 10 min, and then 19 uL of 25% glacial acetic acid is added to stop the reaction. Fluorescence is measured using a CytoFluor II fluorometer (excitation 380 nm/ emission 460 nm). Vildagliptin and solvent controls are added as 30 uL additions, and the assay buffer volume is reduced to 95 uL.

Vildagliptin (LAF-237) Chemical Structure

2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO