Disease relevance of A-78773

• The efficacy of three such inhibitors that have been in clinical trials (zileuton, A-78773 and ZD2138) were evaluated in: 1) ex vivo whole blood assay, 2) dermal Arthus reaction, and 3) functional airway response [1].

High impact information on A-78773

• Polymorphism and crystallization behavior of Abbott-79175, a second-generation 5-lipoxygenase inhibitor [2].
• Stereoselective metabolism of the 5-lipoxygenase inhibitor A-78773 [3].
• Further studies with liver microsomes revealed that glucuronidation of A-78773 was stereoselective and that the R(+) enantiomer was considerably more resistant to conjugation than the S(-) stereoisomer [3].
• Since 78% of the drug plasma AUC following A-78773 administration was accounted for by the R(+) enantiomer, it is reasonable to assume that the majority of the leukotriene inhibition caused by the racemate is attributable to the R(+) enantiomer, A-79175, particularly at the later times [3].
• Orally administered indomethacin, a selective cyclooxygenase inhibitor, and three selective 5-lipoxygenase inhibitors, zileuton, A-78773 and ICI-D-2138 markedly attenuated respective arachidonate pathways with projected ED50 values of < 1-2 mg/kg [4].

Biological context of A-78773

• The importance of leukotrienes as mediators of inflammation and bronchoconstriction was examined with two recently described 5-lipoxygenase inhibitors, zileuton and A-78773 [5].

Anatomical context of A-78773

• A-78773 inhibited a RBL cell lysate 5-lipoxygenase at concentrations 2 orders of magnitude lower than those required to inhibit rabbit reticulocyte 15-lipoxygenase or human platelet 12-lipoxygenase [6].

Analytical, diagnostic and therapeutic context of A-78773

• Furthermore, a single oral administration of either ICI-D-2138 or A-78773 (each 20 mg/kg, po) resulted in persistent inhibition of 5-lipoxygenase pathway for up to 24 hr [4].

References