A Novel Synthetic Anti-Acute Pancreatitis Agent, IS-741

Abstract

A novel synthetic drug, IS-741, inhibited cell adhesion in vitro and neutrophil in vivo. Thus, IS-741 inhibited the magnification of pancreatic lesion as well as progression to multiple organ failure in acute pancreatitis models. Furthermore, IS-741 at identical plasma concentrations equally improved the survival rates in animals of various species with severe acute pancreatitis. Based on these observations, it was considered that IS-741 inhibited tissue destruction by neutrophil after inhibiting neutrophil infiltration into the pancreas or other important organs in acute pancreatitis. It was also considered that IS-741 demonstrated various anti-acute pancreatitis effects by interrupting a vicious cycle of inflammation. Therefore, IS-741 is expected to become a useful drug for treating acute pancreatitis and multiple organ failure in clinical settings.

Efficacy of the Inflammatory Cell Infiltration Inhibitor IS-741 on Colitis Induced by Dextran Sulfate Sodium in the Rat

“…It has also been reported that the inhibition by IS-741 of leukocyte infiltration is based on inhibition of cell adhesion (22,23). IS-741 acts on HL-60 (a human promyelocytic leukemia line) and inhibits the adhesion of HL-60 to vascular endothelial cells (22).…”

Effect of IS-741 on ethionine-induced acute pancreatitis in rats: relation to pancreatic acinar cell regeneration

“…[7][8][9] Therefore, IS-741 may become useful for treating patients with severe acute pancreatitis and MOF. IS-741 has therapeutic effects on acute pancreatitis induced in the rat by using a closed duodenal loop, 10 and on lung injury in rats with cerulein-induced pancreatitis complicated by endotoxemia.…”

“…7-9 IS-741 suppresses various inflammatory events, [7][8][9] and therefore might be clinically useful in treating severe acute pancreatitis and MOF. The present study examined the effect of short-term administration of IS-741 on ethionineinduced pancreatitis in rats as a model of acute necrotizing pancreatitis.…”

A novel diamino-pyridine derivative (IS-741) attenuates rat ileitis induced by trinitrobenzene sulfonic acid

“…14 There have been several studies suggesting that this new anti-inflammatory agent was effective for in-vivo animal inflammatory models. Yotsuya et al 16 reported that IS-741 (0.03 or 0.3mg/kg per h), administered subcutaneously in a rat severe acute pancreatitis model (induced by trypsin and taurocholic acid) could inhibit the development of the pancreatic lesion as well as the progression to multiple organ failure. Liang et al 17 reported that intravenous IS-741 (0.03mg/kg per h) administration for 30 min effectively prevented cerulein-induced pancreatitis and the associated lung injury following an endotoxin challenge.…”

“…[15][16][17][18] However, there are only few reports about the efficacy of leukocyte-endothelial interaction inhibitors against intestinal inflammation. 19 In the present study, we investigated the effects of oral IS-741 on rat experimental ileitis.…”