Background:

LAF-237 is a potent inhibitor of DDP-4 with IC50 value of 2.3 nM [1].
DDP-4 is an antigenic enzyme expressed on the surface of most cell types and is associated with signal transduction, apoptosis and immune regulation [1].
LAF-237 is a specific inhibitor of DDP4 and can reduce glycemia. When tested on Type II diabetes patients, LAF-237 inhibits the inactivation of GLP-1 by DPP-4, allowing GLP-1 to increase the secretion of insulin and decrease glucagon release [2].
In the glucose tolerance test with obese male Zucker rats, LAF-237 can significantly decrease glucose excursion and stimulates insulin secretion. There are 95% inhibition activities of DDP-4 two hours after the injection of LAF-237[3]. Through enhances beta cell replication and reduces apoptosis, LAF-237 increases in the number of beta cell and can sustain for 12 days after washout LAF-237. Also, LAF-237 can protect nerve fiber loss in STZ-induced diabetic adult male Sprague Dawley rats [4].
参考文献:
[1]. Chakraborty S, Rendón-Ramírez A, Ásgeirsson B, et al. The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins. F1000Res, 2013, 2: 286.
[2]. Ahrén B, Landin-Olsson M, Jansson PA, et al. Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. The Journal of Clinical Endocrinology and Metabolism, 2004, 89 (5): 2078–84.
[3] Villhauer EB, et al. 1-[[(3-hydroxy-1-adamantyl) amino] acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties. J Med Chem, 2003, 46(13), 2774-2789.
[4] Duttaroy A, et al. Combination therapy with nateglinide and vildagliptin improves postprandial metabolic derangements in Zucker fatty rats. Eur J Pharmacol, 2011, 650(2-3), 703-707.