Differential effects of FR900482 and FK317 on apoptosis, IL-2 gene expression, and induction of vascular leak syndrome.

@article{Beckerbauer2002DifferentialEO,
  title={Differential effects of FR900482 and FK317 on apoptosis, IL-2 gene expression, and induction of vascular leak syndrome.},
  author={Lois Beckerbauer and Jetze J Tepe and Rebecca A Eastman and Philip F. Mixter and Robert M. Williams and Raymond Reeves},
  journal={Chemistry & biology},
  year={2002},
  volume={9 4},
  pages={427-41}
}
Vascular leak syndrome (VLS) is a harmful side effect that resulted in withdrawal of the antitumor drug FR900482, but not FK317, from clinical trials. Here we present chromatin immunoprecipitation data showing that FK317, like FR900482, crosslinks minor-groove binding proteins to DNA in vivo. However, these drugs differ in how they induce cell death. We demonstrate that, whereas FR900482 induces necrosis, FK317 induces a necrosis-to-apoptosis switch that is drug concentration dependent… CONTINUE READING

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