From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates

@article{MBChB2005FromMT,
  title={From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates},
  author={Ph.D Jackie Walling MBChB},
  journal={Investigational New Drugs},
  year={2005},
  volume={24},
  pages={37-77}
}
• Are multiple intracellular targets better than one? Does inhibition of dihydrofolate reductase (DHFR), thymidylate synthase (TS) or enzymes of the purine biosynthetic pathway confer an advantage? Alternatively, is inhibition of purine biosynthesis a safety liability rather than an advantage? • Can a lipophilic molecule rather than one that uses the folate carrier mechanisms, i.e. the folate binding protein (FBP) and or the reduced folate carrier (RFC), circumvent intrinsic or acquired… CONTINUE READING