The magic of small structure differences in a sodium-glucose cotransporter drug discovery project-14 C-labelled drug candidates in a key-differentiating study

We describe the dramatic differences in the synthesis and physiological and pharmacokinetical profiling of two sodium-glucose cotransporter (SGLT) drug candidates AVE2268 and AVE8887 with very similar chemical structures. It is a classic example of how a radioactive study was able to spare resources in preclinical development prior to entering a costly clinical program. It also demonstrated that radioactive compounds can be used to study differences between two very similar compounds in vivo.

14C synthesis; SGLT; diabetes; pharmacological profiling.