Biochemical and pharmacological properties of a new topical anti-inflammatory compound, 9-phenylnonanohydroxamic acid (BMY 30094).

Abstract	Drugs which block the biosynthesis of leukotrienes and prostaglandins may have potential in the treatment of psoriasis and other skin diseases. The biochemical and anti-inflammatory activity of 9-phenylnonanohydroxamic acid (BMY 30094) is described. BMY 30094 inhibited human neutrophil 5-lipoxygenase with an IC50 of 5.7 microM. BMY 30094 also blocked human platelet cyclooxygenase and lipoxygenase with IC50 values of 15.2 and 15.0 microM, respectively. Topical application of this compound blocked arachidonic acid and 12-O-tetradecanoylphorbol ester-induced mouse skin inflammation with activity comparable to that observed for lonapalene. The topical ED50 for BMY 30094 in the arachidonic acid-induced inflammation model is 2.2 mumoles/ear. In the sub-cutaneous carrageenan sponge assay in rats, BMY 30094 blocked LTB4 and PGE2 production and inhibited neutrophil migration. This compound would be a useful tool to determine the role of arachidonic acid metabolites in the etiology of inflammatory dermatoses.
Authors	K M Tramposch, F C Zusi, S A Marathe, P L Stanley, X Nair, S A Steiner, J W Quigley
Journal	Agents and actions (Agents Actions) Vol. 30 Issue 3-4 Pg. 443-50 (Jun 1990) ISSN: 0065-4299 [Print] Switzerland
PMID	2117339 (Publication Type: Journal Article)
Chemical References	Anti-Inflammatory Agents, Non-Steroidal Arachidonic Acids Eicosanoids Hydroxamic Acids 9-phenylnonanohydroxamic acid Arachidonic Acid Carrageenan Arachidonate 12-Lipoxygenase Arachidonate 5-Lipoxygenase Prostaglandin-Endoperoxide Synthases Tetradecanoylphorbol Acetate
Topics	Administration, Cutaneous Animals Anti-Inflammatory Agents, Non-Steroidal (pharmacology) Arachidonate 12-Lipoxygenase (metabolism) Arachidonate 5-Lipoxygenase (metabolism) Arachidonic Acid Arachidonic Acids Carrageenan Chromatography, High Pressure Liquid Eicosanoids (metabolism) Exudates and Transudates (drug effects) Female Hydroxamic Acids Inflammation (chemically induced, drug therapy) Male Mice Molecular Structure Prostaglandin-Endoperoxide Synthases (metabolism) Rats Rats, Inbred Strains Tetradecanoylphorbol Acetate

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