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Chemical Compound Review

Miraclid     9-(2-furyl)-8,10- dioxaspiro[5.5]undec-3-ene

Synonyms: Ulinastatin, Urinastatin, UTI68, Uti(68), MR 20, ...
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Disease relevance of Acid-stable protease inhibitor


Psychiatry related information on Acid-stable protease inhibitor


High impact information on Acid-stable protease inhibitor

  • Urinary trypsin inhibitor (UTI) has a multipotent inhibitory effect on proteases such as trypsin, chymotrypsin, plasmin, human leukocyte elastase, or hyaluronidase [9].
  • The present study was undertaken to determine whether highly purified human urinary trypsin inhibitor (UTI) efficiently inhibits the soluble and the tumor cell receptor-bound plasmin [1].
  • Suppression of urokinase expression and invasiveness by urinary trypsin inhibitor is mediated through inhibition of protein kinase C- and MEK/ERK/c-Jun-dependent signaling pathways [10].
  • Urinary trypsin inhibitor (UTI) forms membrane complexes with UTI-binding proteins (UTI-BPs) and initiates modulation of urokinase-type plasminogen activator (uPA) expression, which results in UTI-mediated suppression of cell invasiveness [3].
  • The cell surface receptor-bound UTI derived from ITI may be the result of the limited proteolysis on the cell surface [11].

Chemical compound and disease context of Acid-stable protease inhibitor


Biological context of Acid-stable protease inhibitor


Anatomical context of Acid-stable protease inhibitor


Associations of Acid-stable protease inhibitor with other chemical compounds

  • A model for cell surface UTI formation is proposed in which ITI binding to cells from serum used for the culture is followed by the limited proteolysis by trace amounts of active serine proteases, to form cell-surface receptor-bound UTI and the H-chains intercalated into cell surface HA [11].
  • The purpose of this study is to determine whether ITI binding to tumor cell surface is mediated by urinary trypsin inhibitor (UTI)-receptor or cell-associated hyaluronic acid (HA) [11].
  • Thus, ulinastatin inhibits arachidonate PHS metabolism by inhibiting new induction of PHS-2 at the mRNA level, which is a novel pharmacologic action of this substance [16].
  • The experimental group was divided into a control group, a UTI (urinary trypsin inhibitor) group and a GM (gabexate mecilate) group [23].
  • Protease inhibitors such as gabexate mesilate (GM) and ulinastatin (UTI) have been shown to have various beneficial effects by inhibiting the activation of leukocytes, but the mechanism for this has yet to be fully elucidated [24].

Gene context of Acid-stable protease inhibitor


Analytical, diagnostic and therapeutic context of Acid-stable protease inhibitor


  1. Inhibition of the soluble and the tumor cell receptor-bound plasmin by urinary trypsin inhibitor and subsequent effects on tumor cell invasion and metastasis. Kobayashi, H., Shinohara, H., Takeuchi, K., Itoh, M., Fujie, M., Saitoh, M., Terao, T. Cancer Res. (1994) [Pubmed]
  2. Isolation of urinary trypsin inhibitor-like inhibitor from human lung cancer tissue. Okumichi, T., Nishiki, M., Takasugi, S., Toki, N., Ezaki, H. Cancer Res. (1984) [Pubmed]
  3. Characterization of binding properties of urinary trypsin inhibitor to cell-associated binding sites on human chondrosarcoma cell line HCS-2/8. Hirashima, Y., Kobayashi, H., Suzuki, M., Tanaka, Y., Kanayama, N., Fujie, M., Nishida, T., Takigawa, M., Terao, T. J. Biol. Chem. (2001) [Pubmed]
  4. Comparative studies on the analysis of urinary trypsin inhibitor (ulinastatin) preparations. Matsuno, Y.K., Nakamura, H., Kakehi, K. Electrophoresis (2006) [Pubmed]
  5. Effect of protease inhibitor on ischemia/reperfusion injury of the rat liver. Li, X.K., Matin, A.F., Suzuki, H., Uno, T., Yamaguchi, T., Harada, Y. Transplantation (1993) [Pubmed]
  6. Change in the equilibrium of the levels of free and bound forms of alpha1-microglobulin and ulinastatin in patients with mood disorders. Uegaki, J., Shikimi, T., Kaku, K., Takaori, S. Neuropsychobiology (2002) [Pubmed]
  7. Significant decreases of ulinastatin-like immunoreactive substance in the cerebrospinal fluid of patients with dementia. Shikimi, T., Inagaki, T., Ishino, H., Kobayashi, S., Matsubara, K., Okunishi, H., Takaori, S. Neuropsychobiology (1997) [Pubmed]
  8. Changes in the ratio of urinary alpha 1-microglobulin to ulinastatin levels in patients with Alzheimer-type dementia and vascular dementia. Inagaki, T., Shikimi, T., Ishino, H., Okunishi, H., Takaori, S. Psychiatry and clinical neurosciences. (1995) [Pubmed]
  9. Inhibition of tumor cell invasion through matrigel by a peptide derived from the domain II region in urinary trypsin inhibition. Kobayashi, H., Gotoh, J., Kanayama, N., Hirashima, Y., Terao, T., Sugino, D. Cancer Res. (1995) [Pubmed]
  10. Suppression of urokinase expression and invasiveness by urinary trypsin inhibitor is mediated through inhibition of protein kinase C- and MEK/ERK/c-Jun-dependent signaling pathways. Kobayashi, H., Suzuki, M., Tanaka, Y., Hirashima, Y., Terao, T. J. Biol. Chem. (2001) [Pubmed]
  11. Inter-alpha-trypsin inhibitor bound to tumor cells is cleaved into the heavy chains and the light chain on the cell surface. Kobayashi, H., Gotoh, J., Hirashima, Y., Terao, T. J. Biol. Chem. (1996) [Pubmed]
  12. Inhibitory effects of ulinastatin on the production of cytokines: implications for the prevention of septicemic shock. Endo, S., Inada, K., Taki, K., Hoshi, S., Yoshida, M. Clinical therapeutics. (1990) [Pubmed]
  13. Ulinastatin shows preventive effect on post-endoscopic retrograde cholangiopancreatography pancreatitis in a multicenter prospective randomized study. Fujishiro, H., Adachi, K., Imaoka, T., Hashimoto, T., Kohge, N., Moriyama, N., Suetsugu, H., Kawashima, K., Komazawa, Y., Ishimura, N., Ishihara, S., Amano, Y., Kinoshita, Y. J. Gastroenterol. Hepatol. (2006) [Pubmed]
  14. Protective effect of human ulinastatin against gentamicin-induced acute renal failure in rats. Nakakuki, M., Yamasaki, F., Shinkawa, T., Kudo, M., Watanabe, M., Mizota, M. Can. J. Physiol. Pharmacol. (1996) [Pubmed]
  15. New endoscopic treatment for chronic pancreatitis, using contrast media containing ulinastatin and prednisolone. Ohwada, M., Watanabe, N., Maeda, M., Gotoh, M., Teramoto, J., Moriya, H., Nakajima, T., Okamoto, T., Tsuji, N., Kobayashi, D., Niitsu, Y. J. Gastroenterol. (1997) [Pubmed]
  16. Ulinastatin, an elastase inhibitor, inhibits the increased mRNA expression of prostaglandin H2 synthase-type 2 in Kawasaki disease. Zaitsu, M., Hamasaki, Y., Tashiro, K., Matsuo, M., Ichimaru, T., Fujita, I., Tasaki, H., Miyazaki, S. J. Infect. Dis. (2000) [Pubmed]
  17. Urinary trypsin inhibitor suppresses the production of interstitial procollagenase/proMMP-1 and prostromelysin 1/proMMP-3 in human uterine cervical fibroblasts and chorionic cells. Imada, K., Ito, A., Kanayama, N., Terao, T., Mori, Y. FEBS Lett. (1997) [Pubmed]
  18. Protective effects of human urinary trypsin inhibitor against trypsin-induced relaxation in rat aorta. Ooka, T., Hatano, Y., Yamamoto, M., Ogawa, K., Saika, S. Crit. Care Med. (1996) [Pubmed]
  19. Urinary trypsin inhibitor prevents uterine muscle contraction by inhibition of Ca++ influx. Kanayama, N., el Maradny, E., Halim, A., Liping, S., Maehara, K., Kajiwara, Y., Terao, T. Am. J. Obstet. Gynecol. (1995) [Pubmed]
  20. Protease inhibitors (gebexate mesylate and ulinastatin) stimulate intracellular chemiluminescence in human neutrophils. Nishijima, J., Hiraoka, N., Murata, A., Oka, Y., Kitagawa, K., Tanaka, N., Toda, H., Mori, T. J. Leukoc. Biol. (1992) [Pubmed]
  21. Inhibition of lipopolysaccharide-induced tissue factor expression in monocytes by urinary trypsin inhibitor in vitro and in vivo. Molor-Erdene, P., Okajima, K., Isobe, H., Uchiba, M., Harada, N., Shimozawa, N., Okabe, H. Thromb. Haemost. (2005) [Pubmed]
  22. Effects of urinary trypsin inhibitor on the invasion of reconstituted basement membranes by ovarian cancer cells. Kobayashi, H., Fujie, M., Shinohara, H., Ohi, H., Sugimura, M., Terao, T. Int. J. Cancer (1994) [Pubmed]
  23. The effect of protease inhibitor on reperfusion injury after unilateral pulmonary ischemia. Horiguchi, T., Harada, Y. Transplantation (1993) [Pubmed]
  24. Mechanism of the inhibitory effect of protease inhibitor on tumor necrosis factor alpha production of monocytes. Aosasa, S., Ono, S., Mochizuki, H., Tsujimoto, H., Ueno, C., Matsumoto, A. Shock (2001) [Pubmed]
  25. Ulinastatin reduces elevation of cytokines and soluble adhesion molecules during cardiac surgery. Kawamura, T., Inada, K., Akasaka, N., Wakusawa, R. Canadian journal of anaesthesia = Journal canadien d'anesthésie. (1996) [Pubmed]
  26. Inhibition of neutrophil elastase-induced interleukin-8 gene expression by urinary trypsin inhibitor in human bronchial epithelial cells. Nakamura, H., Abe, S., Shibata, Y., Sata, M., Kato, S., Saito, H., Hino, T., Takahashi, H., Tomoike, H. Int. Arch. Allergy Immunol. (1997) [Pubmed]
  27. Antioxidative role of urinary trypsin inhibitor in acute lung injury induced by lipopolysaccharide. Inoue, K., Takano, H., Yanagisawa, R., Sakurai, M., Shimada, A., Sato, H., Kato, Y., Yoshikawa, T. Int. J. Mol. Med. (2005) [Pubmed]
  28. Attenuation of graft ischemia-reperfusion injury by urinary trypsin inhibitor in mouse intestinal transplantation. Yu, J.R., Yan, S., Liu, X.S., Wu, Y.J., Fu, P.F., Wu, L.H., Zheng, S.S. World J. Gastroenterol. (2005) [Pubmed]
  29. Identification and characterization of a Kunitz-type protease inhibitor in ascites fluid from patients with ovarian carcinoma. Kobayashi, H., Hirashima, Y., Sun, G.W., Ohi, H., Fujie, M., Terao, T. Int. J. Cancer (2000) [Pubmed]
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