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Farnesyltransferase Inhibitors

Anti-Ras or Anticancer Drugs?

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Signaling Networks and Cell Cycle Control

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Oncogenic ras mutations and aberrant Ras function are important in many human tumors, so blocking the activity of oncogenic Ras has been a significant priority in recent drug discovery efforts toward novel cancer chemotherapeutic agents. These efforts have included attempts designed specifically to inhibit the active, guanosine triphosphate (GTP)-bound form of Ras, to reduce the total amount of GTP-bound Ras, to interfere with Ras binding to its downstream targets or to interfere with those targets themselves, or to prevent Ras from associating with the plasma membrane. Of these approaches, the last has been the most successful to date. Ras and other farnesylated proteins require modification by a farnesyl isoprenoid lipid for correct subcellular localization and biological activity. Farnesyltransferase (FTase), the enzyme that attaches the isoprenoid to the C-terminus of Ras, has been a target for rational drug design since its cloning in 1991, and FTase inhibitors (FTIs) are now in early phases of clinical trials as anticancer agents.

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Authors
  1. Adrienne D. Cox
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  2. Channing J. Der
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Editors and Affiliations

  1. Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA

    J. Silvio Gutkind PhD

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Cox, A.D., Der, C.J. (2000). Farnesyltransferase Inhibitors. In: Gutkind, J.S. (eds) Signaling Networks and Cell Cycle Control. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-218-0_28

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  • DOI: https://doi.org/10.1007/978-1-59259-218-0_28

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