Abstract
Evasion of apoptosis is one of the six initially proposed hallmarks of cancer, and as such, a method to detect apoptosis in a tumour would be of considerable interest in both clinical trials of new cancer therapeutics, as well as for routine patient management. Activation of caspase-3/7 is a key biomarker of cellular apoptosis. Herein we describe the design, synthesis and initial characterisation of the first pyrimidoindolone compound for detection of caspase-3/7 activation using positron emission tomography.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkynes / chemical synthesis
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Alkynes / chemistry
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Animals
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Caco-2 Cells
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Caspase 3 / metabolism*
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Caspase 7 / metabolism*
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Chromatography, High Pressure Liquid
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Enzyme Activation
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Humans
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Indoles / blood
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Indoles / chemical synthesis*
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Indoles / chemistry
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Indoles / urine
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Inhibitory Concentration 50
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Liver / metabolism
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Mice
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Models, Biological
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Pyrimidines / blood
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Pyrimidines / chemical synthesis*
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Pyrimidines / chemistry
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Pyrimidines / urine
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Tissue Distribution
Substances
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8'-(2-(((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methoxy)methyl)pyrrolidin-1-ylsulfonyl)-2'H-spiro(cyclopentane-1,3'-pyrimido(1,2-a)indol)-10'(4'H)-one
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Alkynes
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Indoles
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Pyrimidines
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Caspase 3
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Caspase 7