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Chemical Compound Review

TAK-683     (5S)-6-[6-[(1E,3R,5Z)-3- hydroxyundeca-1,5...

Synonyms: SureCN1894359, DCL000655, DNC001479, ZINC04489632, U-75302, ...
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Disease relevance of U 75302


High impact information on U 75302

  • Our data also showed that both LTB4, a product of 5-LOX and LTB4 receptor antagonist U-75302 were able to prevent AA861 and REV5901 on induction of apoptosis [2].
  • In rats pretreated with the LTB4 receptor antagonist, U-75302, GFR and RBF remained depressed to levels no different than in animals which received NTS alone [3].
  • On the other hand, the leukotriene (LT) B(4) receptor antagonist U-75302, the LTD(4) receptor antagonists LY-171883 and MK-571, and the cysteinyl-LT receptor antagonist REV-5901 also inhibit cell proliferation and [(3)H]-thymidine incorporation in a concentration-dependent manner, and delay the RAW 264.7 cell cycle [4].
  • Pre-treatment with transforming growth factor-beta1 enhanced both stimulated leukotriene synthesis and the inhibitory effect of U-75302 and MK886 on IL-10 release from DCs [5].
  • In contrast, U-75302 increased zymosan-stimulated release of IL-12 p40 by approximately 23% [5].

Biological context of U 75302


Anatomical context of U 75302

  • Histopathological analysis of pups treated with 1.5 mg U-75302/100 g body wt revealed fewer neutrophils in the pulmonary interstitium (198 vs. 218 mm-2, P < 0.05) [6].
  • Doses of U-75302 (1.0, 10.0 and 30.0 mg/kg) administered orally produced 12.2%, (p greater than 0.05), 43.2% (p less than 0.05), and 61.1% (p less than 0.05) inhibition, respectively, of the antigen-induced influx of eosinophils into the bronchial lumen [1].

Gene context of U 75302

  • In a second series of experiments, pups exposed to 95% oxygen (and 21% oxygen controls) were treated with a specific LTB4 antagonist (U-75302), at either 0.5, 1.5 or 3.0 mg 100 g body wt to ascertain if LTB4 played a role in either neutrophil recruitment or oedema formation in the immature lung [6].

Analytical, diagnostic and therapeutic context of U 75302

  • The number of neutrophils recovered in bronchoalveolar lavage fluid was significantly reduced, compared to vehicle-treated pups, in pups treated with U-75302, at both 1.5 and 3.0 mg/100 g body wt but not 0.5 mg/100 g body wt [6].


  1. Effect of the selective leukotriene B4 antagonist U-75302 on antigen-induced bronchopulmonary eosinophilia in sensitized guinea pigs. Richards, I.M., Griffin, R.L., Oostveen, J.A., Morris, J., Wishka, D.G., Dunn, C.J. Am. Rev. Respir. Dis. (1989) [Pubmed]
  2. Increased 5-lipoxygenase expression and induction of apoptosis by its inhibitors in esophageal cancer: a potential target for prevention. Hoque, A., Lippman, S.M., Wu, T.T., Xu, Y., Liang, Z.D., Swisher, S., Zhang, H., Cao, L., Ajani, J.A., Xu, X.C. Carcinogenesis (2005) [Pubmed]
  3. Hemodynamic role of arachidonate 12- and 5-lipoxygenases in nephrotoxic serum nephritis. Wu, S.H., Bresnahan, B.A., Lianos, E.A. Kidney Int. (1993) [Pubmed]
  4. Role of 5-lipoxygenase pathway in the regulation of RAW 264.7 macrophage proliferation. Nieves, D., Moreno, J.J. Biochem. Pharmacol. (2006) [Pubmed]
  5. Leukotrienes modulate cytokine release from dendritic cells. Jozefowski, S., Biedroń, R., Bobek, M., Marcinkiewicz, J. Immunology (2005) [Pubmed]
  6. Oxygen-induced lung injury in the pre-term guinea pig: the role of leukotriene B4. Phillips, G.J., Mohammed, W., Kelly, F.J. Respiratory medicine. (1995) [Pubmed]
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