Pharmacophore Reassignment for Induction of the Immunosurveillance Cytokine TRAIL1. (18th May 2014)

• Record Type: Journal Article
• Authors: Jacob, Nicholas T.; Lockner, Jonathan W.; Kravchenko, Vladimir V.; Janda, Kim D.
• Is Part Of: Angewandte Chemie. Volume 126:Number 26(2014)
• Page Start: 6746
• Page End: 6749
• Publication Date: 2014-05-18
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201402133
• Languages: English
• ISSNs: 0044-8249

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) is an immunosurveillance cytokine that kills cancer cells but demonstrates little toxicity against normal cells. While investigating the TRAIL‐inducing imidazolinopyrimidinone TIC10, a misassignment of its active structure was uncovered. Syntheses of the two isomers, corresponding to the published and reassigned structures, are reported. The ability of each to induce TRAIL expression in macrophages was investigated and it was found that only the compound corresponding to the reassigned structure shows the originally reported activity; the compound corresponding to the published structure is inactive. Importantly, this structural reassignment has furnished a previously unknown antitumor pharmacophore.</p> </abstract>