生物活性

• 描述Type 2 diabetes mellitus (T2DM) is a growing and serious global health problem. Pharmacological inhibition of the sodium–glucose cotransporter-2 (SGLT2) increases urinary glucose excretion, decreasing plasma glucose levels in an insulin-independent manner. PF-04971729 is a potent and selective SGLT2 inhibitor with IC₅₀ value of 0.877 nM for h-SGLT2 and it has a 2000-fold increase in selectivity for human SGLT2 over SGLT1 in vitro. Diseases or conditions that can be ameliorated by inhibition of SGLT2 with PF-04971729 include: Type II diabetes, diabetic nephropathy, insulin resistance syndrome, hyperglycemia, hyperinsulinemia, hyperlipidemia, impaired glucose tolerance, obesity (including weight control or weight maintenance), hypertension and reducing the level of blood glucose. PF-04971729 can also be used for treating analogous diseases or conditions in animals. PF-04971729 is rapidly absorbed in preclinical species after oral administration, and it is characterized by low clearance and a moderate steady-state distribution volume. PF-04971729 is well absorbed in humans and eliminated largely via glucuronidation. PF-04971729 improved glycemic control, body weight and blood pressure in 328 patients with T2DM suboptimally controlled on metformin, and was well-tolerated^[3].