Original Articles2,4,6-Trihydroxy-α-p-methoxyphenylacetophenone (Compound D-58) Is a Potent Inhibitor of Allergic ReactionsMalaviya, Ravi1*; Vassilev, Alexei2; Uckun, Fatih M.3,4Author Information Departments of 1Allergy and Inflammatory Diseases, 2Biochemistry, and 3Immunology and 4Drug Discovery Program, Parker Hughes Institute, St. Paul, MN. *Address for correspondence: Parker Hughes Institute, 2665 Long Lake Road, Suite 330, St. Paul, MN 55113, USA; e-mail: [email protected] American Journal of Therapeutics: November-December 2001 - Volume 8 - Issue 6 - p 417-424 Buy Abstract The authors investigated the effects of 2,4,6-trihydroxy-α-p-methoxyphenylacetophenone (compound D-58), a potent inhibitor of protein tyrosine kinases SYK and Bruton's tyrosine kinase (BTK), on IgE receptor/FcεRI-triggered mast cell–mediated acute allergic responses in vitro and in vivo. Compound D-58 abrogated IgE receptor/FcεRI–mediated SYK and BTK activation as well as calcium mobilization in mast cells. Mast-cell degranulation and leukotriene (LT) C4 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. © 2001 Lippincott Williams & Wilkins, Inc.