Design, synthesis and initial characterisation of a radiolabelled [(18)F]pyrimidoindolone probe for detecting activated caspase-3/7

Org Biomol Chem. 2015 May 21;13(19):5418-23. doi: 10.1039/c5ob00058k.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemical synthesis
  • Alkynes / chemistry
  • Animals
  • Caco-2 Cells
  • Caspase 3 / metabolism*
  • Caspase 7 / metabolism*
  • Chromatography, High Pressure Liquid
  • Enzyme Activation
  • Humans
  • Indoles / blood
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / urine
  • Inhibitory Concentration 50
  • Liver / metabolism
  • Mice
  • Models, Biological
  • Pyrimidines / blood
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Pyrimidines / urine
  • Tissue Distribution

Substances

  • 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
  • Alkynes
  • Indoles
  • Pyrimidines
  • Caspase 3
  • Caspase 7