Sodium Glucose cotransporters <unk>  are proteins that occur primarily in the kidneys and play an important role in maintaining glucose balance in the blood.<unk>  and<unk>  are the two most known<unk>  of this family.<unk>  is the major transport protein and promotes reabsorption from the glomerular filtration glucose back into circulation and is responsible for approximately 90% of the kidney's glucose reabsorption.<unk>  is mainly expressed in the kidneys on the epithelial cells lining the first segment of the proximal convoluted tubule. By inhibiting<unk> , gliflozins prevent the kidneys' reuptake of glucose from the glomerular filtrate and subsequently lower the glucose level in the blood and promote the excretion of glucose in the urine (glucosuria). Reabsorption of glucose in the nephron The mechanism of action on a cellular level is not well understood. Work is underway to define this mechanism as a prodiuretic with great promise. However, it has been shown that binding of different sugars to the glucose site affects the orientation of the aglycone in the access vestibule. So when the aglycone binds it affects the entire inhibitor. Together these mechanisms lead to a synergistic interaction. Therefore, variations in the structure of both the sugar and the aglycone are crucial for the pharmacophore of<unk> s. Dapagliflozin is an example of an<unk> , it is a competitive, highly selective inhibitor of<unk>  It acts via selective and potent inhibition of<unk> 2, and its activity is based on each patient's underlying blood sugar control and kidney function. The results are decreased kidney reabsorption of glucose, glucosuria effect increases with higher level of glucose in the blood circulation. Therefore, dapagliflozin reduces the blood glucose concentration with a mechanism that is independent of insulin secretion and sensitivity, unlike many other antidiabetic medications. Functional pancreatic β-cells are not necessary for the activity of the medication so it is convenient for patients with diminished β-cell function. Sodium and glucose are co-transported by the<unk> 2 protein into the tubular epithelial cells across the brush-border membrane of the proximal convoluted tubule. This happens because of the sodium gradient between the tubule and the cell and therefore provides a secondary active transport of glucose. Glucose is later reabsorbed by passive transfer of endothelial cells into the interstitial glucose transporter protein. + TABLE 1: Where are<unk>  expressed?<unk> Expressed in human tissues<unk>  Intestine, trachea, kidney, heart, brain, testis, prostate<unk>  Kidney, brain, liver, thyroid, muscle, heart Ratios of activity between<unk>  and<unk>  may be helpful in defining expression.
SGLT2 inhibitor
Chloride channel opener
COX-2 inhibitor
CYP17A1 inhibitor
Norepinephrine–dopamine disinhibitor
Beta-adrenergic agonist
Reuptake inhibitor
Protein kinase inhibitor