SUMMARY. Sodium-GLucose Cotransporter 2 (SGLT2) inhibitors, known as gliflozins, are the new effective class of hypoglycemic drugs. This study has revealed the major variability in the pockets of target site for all human SLC5 family members and confirmed possibility for SGLT2 selective inhibition. Considering uniqueness of the site, the virtual screening of Enamine Ltd chemical space identifies 36 perspective inhibitors of SGLT2. The ranking of selected compounds based on docking scorring and binding energies identified 5 leaders with predicted activity comparable with known approved drugs. For the first time, the compounds Z2195993226 and Z2195993230 were identified as potential gliflozins. One more compound, Z1494829516 (Puerarin), previously known as an autophagy inducer, ferroptosis inhibitor, cardioprotector, antioxidant, antiinflammatory and antipyretic, was proposed as potential gliflozin. Compound Z2417819595 was excluded from the list of possible SGLT2 inhibitors based on structural consideration. Furthermore, Z2235801995 was identified as the active compound of FDA approved gliflozin NVOKAMET (FDA ID: 4129180), confirming correctness of screening protocol.
Keywords: diabetes, hyperglycemia, gliflozin, inhibitors, SLC5A2, SGLT2, virtual screening
