Mizagliflozin (GSK-1614235 free base) is a sodium-glucose transporter inhibitor( Ki of 27 nM for human SGLT1). Mizagliflozin displays 303-fold selectivity over SGLT2. Mizagliflozin is used as an antidiabetic drug that can modify postprandial blood glucose excursion. Mizagliflozin also exhibits potential in the amelioration of chronic constipation.

SGLT2 (human):8170 nM(ki), SGLT1 (human):(ki)27 nM

Mizagliflozin, a novel selective sodium glucose co-transporter 1 (SGLT1) inhibitor, for the amelioration of chronic constipation.?Mizagliflozin's inhibitory activity against SGLTs was evaluated by an in vitro assay of cells transiently expressing SGLTs.?The safety profile of an initial single dose (2-160mg, orally) and multiple doses (2-20mg, orally, once daily immediately prior to breakfast on Days 1 and 13, and three times daily immediately prior to every meal on Days 3-12) of mizagliflozin was determined by performing a phase I study in healthy male subjects.?In addition, the effect of mizagliflozin and lubiprostone on fecal wet weight was compared using a dog model of loperamide-induced constipation and rat model of low-fiber-diet-induced constipation.?Mizagliflozin potently inhibited human SGLT1 in a highly selective manner.?The results of the phase I study showed mizagliflozin increased stool frequency and loosened stool consistency;?these effects increased progressively with an increase in the dosage and the number of doses of mizagliflozin.?In addition, the oral administration of mizagliflozin increased fecal wet weight in a dog model of loperamide-induced constipation and a rat model of low-fiber-diet-induced constipation, similar to lubiprostone.?The potential use of a novel selective SGLT1 inhibitor, mizagliflozin, for the amelioration of chronic constipation[1].