These authors contributed equally to this work.
Pharmacophore Reassignment for Induction of the Immunosurveillance Cytokine TRAIL†
Article first published online: 18 MAY 2014
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Volume 126, Issue 26, pages 6746–6749, June 23, 2014
How to Cite
Jacob, N. T., Lockner, J. W., Kravchenko, V. V. and Janda, K. D. (2014), Pharmacophore Reassignment for Induction of the Immunosurveillance Cytokine TRAIL. Angew. Chem., 126: 6746–6749. doi: 10.1002/ange.201402133
We thank Josh Foote for the artwork appearing in the Table of Contents entry for this communication. We are grateful to Prof. Arnold Rheingold and Dr. Curtis E. Moore (UCSD) for X-ray crystallographic analyses.
- Issue published online: 20 JUN 2014
- Article first published online: 18 MAY 2014
- Manuscript Revised: 7 MAR 2014
- Manuscript Received: 5 FEB 2014
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.