1616632-79-1Relevant academic research and scientific papers
Pharmacophore reassignment for induction of the immunosurveillance cytokine TRAIL
Jacob, Nicholas T.,Lockner, Jonathan W.,Kravchenko, Vladimir V.,Janda, Kim D.
, p. 6628 - 6631 (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. Setting the record straight: An investigation of an imidazolinopyrimidinone (TIC10) reported to induce expression of the immunosurveillance cytokine TRAIL led to a constitutional reassignment of the active pharmacophore. Analysis of TRAIL induction in macrophages revealed the reported structure to be inactive. The structural identity of the active compound was established. The active compound was then synthesized and its activity confirmed.
PHARMACOPHORE FOR TRAIL INDUCTION
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Paragraph 0071; 0072; 0073; 0074; 0075; 0076; 0077, (2017/05/07)
There are disclosed imidazolinopyrimidinone compounds that have activity to induce TRAIL gene expression in macrophages. There is further disclosed a method for treating various cancers comprising administering effective amounts of an imidazolinopyrimidin
