fluoro-Dapagliflozin

The Uses of fluoro-Dapagliflozin

fluoro-Dapagliflozin is a selective sodium/glucose cotransporter (SGLT) inhibitor that blocks glucose transport with about 100-fold selectivity for SGLT2.

Biological Activity

ki: 5.3 and 330 nm for sglt2 and sglt1, respectivelyfluoro-dapagliflozin is a selective sodium-glucose cotransporter (sglt) inhibitor.human na(+)-d-glucose cotransporter (hsglt) inhibitors constitute the newest class of diabetes drugs, blocking up to in-vivo 50% of renal glucose reabsorption.

in vitro

dapagliflozin and fluoro-dapagliflozin could block glucose transport and glucose-coupled currents with around 100-fold specificity for hsglt2 over hsglt1. it was found that phlorizin and galacto-dapagliflozin rapidly dissociated from sglt2, while fluoro-dapagliflozin dissociated from hsglt2 at a rate 10-fold slower. in contrast, fluoro-dapagliflozin could quickly dissociate from hsglt1 [1].

in vivo

dapagliflozin, the close analog of fluoro-dapagliflozin, could acutely induce renal glucose excretion in normal and diabetic rats, improve glucose tolerance in normal rats, and reduce hyperglycemia in zucker diabetic fatty at doses ranging from 0.1 to 1.0 mg/kg. moreover, the once-daily dapagliflozin treatment was able to significantly lower fasting and fed glucose levels and led to a significant increase in glucose utilization rate [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] han, s. ,hagan, d.l.,taylor, j.r., et al. dapagliflozin, a selective sglt2 inhibitor, improves glucose homeostasis in normal and diabetic rats. diabetes 57, 1723-1729 (2008).
[3] ferrannini e, ramos sj, salsali a, tang w, list jf. dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. diabetes care. 2010 oct;33(10):2217-24.