Preclinical and clinical pharmacodynamic assessment of L-778,123, a dual inhibitor of farnesyl:protein transferase and geranylgeranyl:protein transferase type-I.

@article{Lobell2002PreclinicalAC,
  title={Preclinical and clinical pharmacodynamic assessment of L-778,123, a dual inhibitor of farnesyl:protein transferase and geranylgeranyl:protein transferase type-I.},
  author={Robert B. Lobell and Dongming Liu and Carolyn A. Buser and Joseph Davide and Elizabeth Depuy and Kelly Hamilton and Kenneth S. Koblan and Yih Hwai Lee and Scott D. Mosser and Sherri L. Motzel and James L Abbruzzese and Charles S. Fuchs and Eric K. Rowinsky and Eric H. Rubin and Sunil Dutta Sharma and Paul J. Deutsch and Kathryn E. Mazina and Briggs W. Morrison and Lynne Wildonger and S Yao and Nancy E. Kohl},
  journal={Molecular cancer therapeutics},
  year={2002},
  volume={1 9},
  pages={747-58}
}
Farnesyl:protein transferase (FPTase) inhibitors were developed as anti-Ras drugs, but they fail to inhibit Ki-Ras activity because Ki-Ras can be modified by geranylgeranyl:protein transferase type-I (GGPTase-I). L-778,123, an inhibitor of FPTase and GGPTase-I, was developed in part because it can completely inhibit Ki-Ras prenylation. To support the clinical development of L-778,123, we developed pharmacodynamic assays using peripheral blood mononuclear cells (PBMCs) to measure the inhibition… CONTINUE READING