667865-69-2

TS-021 is a dipeptidyl peptidase 4 (DPP-4) inhibitor potentially for the treatment of type 2 diabetes. TS-021 and/or metformin significantly improved glucose tolerance and glucagon-like peptide-1 (GLP-1) level, and TS-021 alone or in combination with metformin significantly increased the plasma insulin level after nutrient ingestion. In the chronic treatment study, TS-021 in combination with metformin significantly lowered the glycosylated hemoglobin level, plasma insulin level, and α-cell-to-β-cell area ratio in pancreatic islets. TS-021 exhibited a significant improvement in glucose tolerance by increasing the plasma insulin level during oral glucose tolerance tests.

TS-021 is a selective，orally active，reversible and long-acting DPP-IV inhibitor，and exhibits significant inhibition selectivity against DPP-8 (> 600 fold)，DPP-9 (> 1200 fold) and other peptidases (> 15,000 fold). TS-021 inhibits DPP-IV activity in human plasma with an IC50 value of 5.34 nM. TS-021 has long-term persistent plasma drug concentration and potent antihyperglycemic activity，and increases in the active form of GLP-1[1][2].

DPP-4

[1] Fukushima H, et al. Synthesis and structure-activity relationships of potent 4-fluoro-2-cyanopyrrolidine dipeptidyl peptidase IV inhibitors. Bioorg Med Chem. 2008 Apr 1;16(7):4093-106. DOI:10.1016/j.bmc.2008.01.016
[2] Tajima A, et al. (2S,4S)-4-Fluoro-1-{[(2-hydroxy-1,1-dimethylethyl)amino]acetyl}-pyrrolidine-2-carbonitrile monobenzenesulfonate (TS-021) is a selective and reversible dipeptidyl peptidase IV inhibitor. Eur J Pharmacol. 2011 Mar 25;655(1-3):99-107. DOI:10.1016/j.ejphar.2011.01.010