title: 2,4,6-Trihydroxy-alpha-p-methoxyphenylacetophenone (Compound D-58) is a potent inhibitor of allergic reactions.
abstract: The authors investigated the effects of 2,4,6-trihydroxy-alpha-p-methoxyphenylacetophenone (compound D-58), a potent inhibitor of protein tyrosine kinases SYK and Bruton's tyrosine kinase (BTK), on IgE receptor/FcepsilonRI-triggered mast cell-mediated acute allergic responses in vitro and in vivo. Compound D-58 abrogated IgE receptor/FcepsilonRI-mediated SYK and BTK activation as well as calcium mobilization in mast cells. Mast-cell degranulation and leukotriene (LT) C(4) release was inhibited by compound D-58 in a concentration-dependent fashion. Notably, compound D-58 prevented the mast cell mediator-induced vascular hyperpermeability in an in vivo murine model of passive cutaneous anaphylaxis as measured by the prevention of extravasation of systemically administered Evans blue dye. The results uniquely indicate that compound D-58 has potent antiallergic properties. Therefore, further development of compound D-58 may provide the basis for new and effective treatment programs for severe allergic disorders.
authors.affiliation: Department of Allergy and Inflammatory Diseases, Parker Hughes Institute, 2665 Long Lake Road, St. Paul, MN 55113, USA. rmalaviya2@ih.org
authors.forename: R
authors.initials: R
authors.lastname: Malaviya
authors.forename: A
authors.initials: A
authors.lastname: Vassilev
authors.forename: F M
authors.initials: FM
authors.lastname: Uckun
mesh_terms: D000098:Acetophenones / Q000494:pharmacology* / Q000627:therapeutic use; D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D006967:Hypersensitivity / Q000188:drug therapy* / Q000517:prevention & control*; D008297:Male; D008407:Mast Cells / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D017455:Receptors, IgE / Q000187:drug effects / Q000378:metabolism
chemical_list: D000098:Acetophenones; D000893:Anti-Inflammatory Agents; D017455:Receptors, IgE; C419484:compound D58; D011505:Protein-Tyrosine Kinases