N3PT(N3-pyridyl thiamine) is a potent and selective transketolase(TK) inhibitor (IC50= 22 nM for Apo-TK) both in vitro and in vivo.IC50 Value: 22 nM( Apo-TK) ; 26 nM (EC50, Cellular TK) [1]Target: transketolasein vitro: N3PT inhibits transketolase activity in a cell based assay. Competitive inhibition of TK by N3PT in cells treated with increasing doses of thiamine, expressed as percentage enzymatic activity (the slope of initial linear range) of controls not treated with compounds [1].in vivo: Tumors were induced in mice at day 0 and mice were then treated at day 7 with vehicle alone or with N3PT [2]. Low-thiamine diet enhances the sensitivity to N3PT inhibition of TK in spleen. Animals were switched to diets containing 16.5 mg/kg (unchanged), 5 mg/kg, 1 mg/kg, or 0 mg/kg thiamine, from a normal chow containing 16.5mg/kg thiamine [1].
[1]. Allen A. Thomas, Josh Ballard, Bryan Bernat. Potent and Selective Thiamine Antagonists That Inhibit Transketolase. [2]. Jeno Gyuris, May Han, Ronan C, N3-pyridyl-thiamine and its use in cancer treatments. Patent Numeber: WO2005094803 A2 [3]. Thomas AA, De Meese J, Le Huerou Y, Non-charged thiamine analogs as inhibitors of enzyme transketolase. Bioorg Med Chem Lett. 2008 Jan 15;18(2):509-12.