Quinazoline thymidylate synthase inhibitors: methods for assessing the contribution of polyglutamation to their in vitro activity.

@article{Jackman1995QuinazolineTS,
  title={Quinazoline thymidylate synthase inhibitors: methods for assessing the contribution of polyglutamation to their in vitro activity.},
  author={Ann L. Jackman and Rosemary Kimbell and Melody J Brown and Lisa Brunton and Frederick Boyle},
  journal={Anti-cancer drug design},
  year={1995},
  volume={10 7},
  pages={555-72}
}
Many quinazoline thymidylate synthase (TS) inhibitors undergo intracellular metabolism to polyglutamate forms which can significantly alter their activity and pharmacodynamics through improved TS inhibition and drug retention. When a series of quinazolines was tested for inhibitory activity towards TS (IC50 0.001-2 microM) and the growth of L1210 cells (IC50 0.005-10 microM), no direct correlation was observed. However, a very good correlation was apparent if a L1210 variant cell line (L1210… CONTINUE READING