Biological Activity
ki = 2 nmgalacto-dapagliflozin is a potent inhibitor of human sglt2.renal glucose transport is mediated by sodium-glucose cotransporters (sglt) 1 and 2. in humans, sglt2 is responsible for the majority of glucose reabsorption in the kidney.
in vitro
it was found that galacto-dapagliflozin was a selective inhibitor of hsglt2, but was less potent than dapagliflozin for both transporters. both phlorizin and galacto-dapagliflozin rapidly dissociated from sglt2, while dapagliflozin and fluoro-dapagliflozin dissociated from hsglt2 at a rate 10-fold slower. dapagliflozin, fluoro-dapagliflozin, and galacto-dapagliflozin dissociated quickly from hsglt1, and phlorizin readily exchanged with dapagliflozin bound to hsglt1 [1].
in vivo
male db/db mice were administered dapagliflozin for 12 weeks. results showed that administration of dapagliflozin could ameliorate hyperglycemia, β-cell damage and albuminuria in db/db mice. serum creatinine, creatinine clearance and blood pressure were not affected by administration of dapagliflozin. dapagliflozin treatment was able to decrease macrophage infiltration in the kidney of db/db mice [2].
References
[1] hummel, c. s.,lu, c.,liu, j., et al. structural selectivity of human sglt inhibitors. american journal of physiology.cell physiology 302(2), c373-c382 (2012).
[2] terami n et al. long-term treatment with the sodium glucose cotransporter 2 inhibitor, dapagliflozin, ameliorates glucose homeostasis and diabetic nephropathy in db/db mice. plos one. 2014 jun 24;9(6):e100777.
[3] merovci a et al. dapagliflozin lowers plasma glucose concentration and improves β-cell function. j clin endocrinol metab. 2015 may;100(5):1927-32.
