-transparent.png){kind=logo}
ONO-4057(5-[2-(2-Carboxyethyl)-3-[6-(4-methoxyphenyl)-5E- hexenyl]oxyphenoxy]valeric acid), an orally active leukotriene B4(LTB4) antagonist, displaced the binding of [3H] LTB4 to the LTB4 receptor in human neutrophil (Ki = 3.7 +/- 0.9 nM). ONO-4057 inhibited the LTB4-induced rise in cytosolic free calcium (the concentration causing 50% inhibition (IC50) = 0.7 +/- 0.3 microM) and inhibited human neutrophil aggregation, chemotaxis or degranulation induced by LTB4 (IC50 = 3.0 +/- 0.1, 0.9 +/- 0.1 and 1.6 +/- 0.1 microM) without showing any agonist activity at concentration up to 30 microM. ONO-4057 did not inhibit fMLP or C5a-induced neutrophil activation at concentrations up to 30 microM. In the in vivo study, ONO-4057 given orally, prevented LTB4-induced transient neutropenia or intradermal neutrophil migration in guinea pig (the dose causing 50% efficacy (ED50) = 25.6mg/kg or 5.3mg/kg). Furthermore, ONO-4057 given topically, suppressed phorbol-12-myristate-13-acetate (PMA)-induced neutrophil infiltration in guinea pig ear (the effective dose = 1 mg/ear). These results indicate that ONO-4057 is a selective and orally active LTB4 antagonist and may be a potential candidate for the treatment of various inflammatory diseases.
K Kishikawa, and
N Tateishi, and
T Maruyama, and
R Seo, and
M Toda, and
T Miyamoto
January 1991,
Advances in prostaglandin, thromboxane, and leukotriene research,
K Kishikawa, and
N Tateishi, and
T Maruyama, and
R Seo, and
M Toda, and
T Miyamoto
February 1999,
Journal of the American Society of Nephrology : JASN,
K Kishikawa, and
N Tateishi, and
T Maruyama, and
R Seo, and
M Toda, and
T Miyamoto
December 2005,
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association,
K Kishikawa, and
N Tateishi, and
T Maruyama, and
R Seo, and
M Toda, and
T Miyamoto
April 1994,
Inflammation,
K Kishikawa, and
N Tateishi, and
T Maruyama, and
R Seo, and
M Toda, and
T Miyamoto
January 1995,
Advances in prostaglandin, thromboxane, and leukotriene research,
K Kishikawa, and
N Tateishi, and
T Maruyama, and
R Seo, and
M Toda, and
T Miyamoto
October 1989,
Inflammation,
K Kishikawa, and
N Tateishi, and
T Maruyama, and
R Seo, and
M Toda, and
T Miyamoto
August 1991,
Prostaglandins, leukotrienes, and essential fatty acids,
K Kishikawa, and
N Tateishi, and
T Maruyama, and
R Seo, and
M Toda, and
T Miyamoto
February 1989,
Prostaglandins,
K Kishikawa, and
N Tateishi, and
T Maruyama, and
R Seo, and
M Toda, and
T Miyamoto
January 1991,
Advances in prostaglandin, thromboxane, and leukotriene research,
K Kishikawa, and
N Tateishi, and
T Maruyama, and
R Seo, and
M Toda, and
T Miyamoto
January 1997,
Advances in experimental medicine and biology,
