Monday, November 23, 2015

Drugs in Clinical Pipeline: GSK-1614235

GSK-1614235 [3-{[3-(4-{[3-(ß-D-Glucopyranosyloxy)-5-isopropyl-1H-pyrazol-4-yl]methyl}-3-methylphenoxy)propyl]amino}-2,2-dimethylpropanamide] is a potent and selective inhibitor of SGLT1. It has inhibition constant (Ki) values of 27 and 8170 nM for human (h) SGLT1 and hSGLT2, respectively. GSK-1614235 is an analog of KGA-2727 and has nearly 2 fold more specificity for SGLT1 than KGA-2727. Also, this specific behaviour towards SGLT1 makes GSK-1614235 an unique inhibitor compared with other molecules that primarily inhibit renal glucose reabsorption via SGLT2 or have dual effects on SGLT1 and SGLT2 [1].

1. Dobbins, R. L.; et. al. Selective sodium-dependent glucose transporter 1 inhibitors block glucose absorption and impair glucose-dependent insulinotropic peptide release. Am J Physiol Gastrointest Liver Physiol 2015, 308(11), G946-G954.
2. Fushimi, N.; et. al. Pyrazole derivatives, medicinal composition containing the same, medicinal use thereof, and intermediate for production thereof. US20090203633A1 (synthesis and activity)