Gosogliptin

Gosogliptin is a potent and selective inhibitor of dipeptidyl peptidase-IV (DPP-IV). IC50 & Target:DPP-IV^[1][2] In Vitro: Gosogliptin (PF-00734200) is a potent, orally active, selective, and competitive inhibitor of DPP-IV, the enzyme mainly responsible for the degradation of the incretin peptides GLP-1 and glucose-dependent insulinotropic polypeptide. Gosogliptin demonstrates greater than 200-fold selectivity over other members of the DPP family (DPP-2, DPP-3, DPP-8, and DPP-9) and the related serine proteases, fibroblast activation protein, aminopeptidase P, and propyl oligopeptidase, enzymes that possess similar catalytic activities. Gosogliptin demonstrates rapid and reversible inhibition of plasma DPP-4 activity when administered orally to rats, dogs, and monkeys. In various nonclinical models, Gosogliptin stimulates insulin secretion and improves glucose tolerance^[2]. In Vivo: The objectives of the present study are to characterize the metabolism, pharmacokinetics, and excretion of [¹⁴C] Gosogliptin in Sprague-Dawley (SD) rats, beagle dogs, and humans. A single dose of [¹⁴C] Gosogliptin is administered orally to intact SD rats (5 mg/kg), beagle dogs (5 mg/kg), and humans (20 mg). After a single oral dose of [¹⁴C] Gosogliptin to SD rats, an overall mean of 97.1% of the administered radioactivity is recovered in the urine, feces, and cage wash over a period of 168 h postdose. The mean cumulative dose recovered in feces is 66.0%. The mean cumulative excretion in the urine is 30.8%. Approximately 95% of the excreted radioactivity recovery occurred in the first 48 h. Mean total recoveries of dosed radioactivity from bile duct-cannulated rats are 29.5% in urine and 62.0% in bile. No gender-related differences are observed in the excretion pattern of radioactivity^[2].