bts-67582 and pimagedine

BTS 67582 (1,1-dimethyl-2-(2-morpholinophenyl) guanidine fumarate) is an insulin-releasing agent currently in phase II clinical trials. Its effect on advanced glycation end product (AGE) formation was measured in the BSA/D-glucose and L-lysine/glucose-6-phosphate assay systems and Amadori product formation was measured in the BSA/D-glucose assay system, following a 3 week incubation period. In the BSA/D-glucose assay system, 200 mM BTS 67582 caused an approximate 70% inhibition in AGE formation (p<0.001), whilst at 20 mM and 2 mM it caused a marginal inhibition (21%, (p<0.001) and 8% respectively). 200 mM and 20 mM aminoguanidine-HCl inhibited AGE formation by 95% and 69% (p<0.001), respectively, whereas 2 mM aminoguanidine-HCl had no significant effect. Tolbutamide (200 microM) and glibenclamide (100 microM) had significant, but only marginal, effects on AGE formation (16% and 17%, respectively, p<0.01). In the BSA/D-glucose assay system 200 mM BTS 67582 and 200 mM aminoguanidine-HCl retarded Amadori product formation by 88% (p<0.001) and 60% (p<0.01), respectively. BTS 67582 at 20 mM and 2 mM was shown to inhibit Amadori product formation by 67% and 57%, respectively, (p<0.01). In the lysine and glucose-6-phosphate assay system 200 mM BTS 67582 and 200 mM aminoguanidine-HCl were shown to inhibit AGE formation by about 70% and 96% (p<0.001), respectively. Tolbutamide (200 microM) and glibenclamide (100 microM) had no significant effect on AGE formation.

Topics: Ferrous Compounds; Glucose; Glucose-6-Phosphate; Glyburide; Glycation End Products, Advanced; Guanidines; Lysine; Serum Albumin, Bovine; Tolbutamide