FK 3311, a cell-permeable and orally available sulfonanilide, is a highly selective inhibitor of cyclooxygenase (COX)-2 with IC 50 value of 1.6 μM.
Cyclooxygenase-2 (COX-2) is a membrane bound enzyme that transfers the electrons from cytochrome c to the catalytic subunit 1. The expression of COX-2 is tightly regulated and induced by different mediators such as cytokine, growth factor, and endotoxin.
FK3311 was shown to selectively inhibit consititutive and inducible COX-2 activity in human platelets and mononuclear cells [1].
The component has also been used extensively in various animal models to study the role of COX-2. In ischemia-reperfusion rat model, administration of FK 3311 via the penile vein can significantly reduce the serum levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and thromboxane (Tx) B2. However, FK 3311 treatment did not reduce the 6-keto-PG F1a levels in these rats[2]. In addition, liver tissue blood flow was remarkably better in the FK3311 treated rat compared with their control group. Histological examination of the livers revealed that FK3311 treatment reduced the hepatic tissue damage and improved the liver graft function [3]. In the canine lung transplantation model, treatment of FK3311 reduced lung damage, neutrophil infiltration into lung, technetium-99m-albumin accumulation and thromboxane B2 level. The lung with FK3311 treatment had better pulmonary gas exchange and hemodynamics [4].
References:
1.Grossman CJ, Wiseman J, Lucas FS, Trevethick MA, Birch PJ. Inhibition of constitutive and inducible cyclooxygenase activity in human platelets and mononuclear cells by NSAIDs and Cox 2 inhibitors. Inflamm Res 1995,44:253-257.
2.Kobayashi M, Takeyoshi I, Kurabayashi M, Matsumoto K, Morishita Y. The effects of a cyclooxygenase-2 inhibitor, FK3311, on total hepatic ischemia-reperfusion injury of the rat. Hepatogastroenterology 2007,54:522-526.
3.Oshima K, Yabata Y, Yoshinari D, Takeyoshi I. The effect of cyclooxygenase (COX)-2 inhibition on ischemia-reperfusion injury in liver transplantation. J Invest Surg 2009,22:239-245.
4.Sunose Y, Takeyoshi I, Tsutsumi H, Ohwada S, Oriuchi N, Matsumoto K, et al. Effect of a cyclooxygenase-2 inhibitor, FK3311, in a canine lung transplantation model. Ann Thorac Surg 2001,72:1165-1171; discussion 1171-1162.