The development of protein farnesyltransferase inhibitors as signaling-based anticancer agents.
The presence of mutated Ras in more that 30% of human cancers has spurred interest in the identification of molecules that can block its uncontrolled signaling function. A particular focus in recent years has been a key posttranslational modification of Ras that places a farnesyl group on a cysteine residue near the C-terminus of the protein. In this chapter we describe recent progress in the design of inhibitors for the enzyme that catalyzes this step, protein farnesyltransferase, and show their potential for blocking oncogenic cell growth.
Drug Discovery Program, H. Lee Moffitt Cancer Center & Research Institute, Departments of Oncology and Biochemistry & Molecular Biology, University of South Florida, Tampa, FL, USA.
Junko
J
Ohkanda
Michelle A
MA
Blaskovich
Saïd M
SM
Sebti
Andrew D
AD
Hamilton
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D017368:Protein Prenylation / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D018631:ras Proteins / Q000378:metabolism*
D004791:Enzyme Inhibitors; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; D018631:ras Proteins