Structure-Guided Development of Selective RabGGTase Inhibitors (pages 4957–4961)
Dr. Robin S. Bon, Dr. Zhong Guo, E. Anouk Stigter, Dr. Stefan Wetzel, Dr. Sascha Menninger, Dr. Alexander Wolf, Dr. Axel Choidas, Prof. Dr. Kirill Alexandrov, Dr. Wulf Blankenfeldt, Prof. Dr. Roger S. Goody and Prof. Dr. Herbert Waldmann
Article first published online: 21 APR 2011 | DOI: 10.1002/anie.201101210
Designing for selectivity: A combination of protein crystal-structure analysis, virtual screening, and synthetic chemistry has been used to develop noncytotoxic inhibitors of RabGGTase (IC50: 42 nM for the example shown; red O, blue N, yellow S) that are selective over FTase and GGTase I. Furthermore, the inhibitors display cellular activity and inhibit cancer cell proliferation.