Inhibition of IgE-mediated N-acetylglucosaminidase and serotonin release from rat basophilic leukemia cells (RBL-2H3) by tenidap: a novel anti-inflammatory agent.
Tenidap [(Z)-5-chloro-2,3-dihydro-3-(hydroxy-2-thienylmethylene)-2-oxo-1H- indole-1-carboxamide] is a novel anti-inflammatory compound of the oxindole class that currently is undergoing clinical evaluation in man. Here we demonstrate that tenidap inhibits (IC50 = approximately 10 microM) IgE-mediated secretion of granule constituents from the rat mast cell tumor line RBL-2H3. The inhibitory effect is rapid in onset, readily reversible, and appears to be unique when compared to a representative selection of other acidic (carboxylic acids, pyrazoles and oxicams) nonsteroidal anti-inflammatory compounds.
Conklyn
M J
MJ
Department of Immunology and Infectious Diseases, Pfizer Central Research, Groton, Conn.
Kadin
S B
SB
Showell
H J
HJ
D000118:Acetylglucosaminidase / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D005089:Exocytosis / Q000187:drug effects; D007073:Immunoglobulin E / Q000037:antagonists & inhibitors*; D007211:Indoles / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D000078183:Oxindoles; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007211:Indoles; D000078183:Oxindoles; D012701:Serotonin; D007073:Immunoglobulin E; C062866:tenidap; D000118:Acetylglucosaminidase