Clinical and Translational Oncology

, Volume 9, Issue 9, pp 563–570 | Cite as

Peptidomimetics in cancer chemotherapy

Educational Series


A summary of the current status of the application of peptidomimetics in cancer therapeutics as an alternative to peptide drugs is provided. Only compounds that are used in therapy or at least under clinical trials are discussed, using inhibitors of farnesyltransferase, proteasome and matrix metalloproteinases as examples.

Key words

Farnesyltransferase inhibitors Ras Metalloproteinase inhibitors Angiogenesis Proteasome inhibitors 


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  1. 1.
    DeLano WL, Ultsch MH, de Vos AM, Wells JA (2000) Convergent solutions to binding at a protein-protein interface. Science 287:1279–1283PubMedCrossRefGoogle Scholar
  2. 2.
    Tarasova NI (2004) Peptides and peptidomimetics as anti-cancer therapeutics. Curr Pharm Design 10:1–3CrossRefGoogle Scholar
  3. 3.
    Walensky LD, Kung AL, Escher I et al (2004) Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science 305:1466–1470PubMedCrossRefGoogle Scholar
  4. 4.
    Reuter CWM, Morgan MA, Bergmann L (2000) Targeting the Ras signaling pathway: a rational, mechanism-based treatment for hematologic malignancies? Blood 96:1655–1669PubMedGoogle Scholar
  5. 5.
    Adjei AA (2001) Ras signaling pathway proteins as therapeutic targets. Curr Pharm Design 7:1581–1594CrossRefGoogle Scholar
  6. 6.
    Downward J (2003) Targeting RAS signalling pathways in cancer therapy. Nature Rev Cancer 3:11–22CrossRefGoogle Scholar
  7. 7.
    Russo P, Loprevite M, Cesario A, Ardizzoni A (2004) Farnesylated proteins as anticancer drug targets: from laboratory to the clinic. Curr Med Chem Anticancer Agents 4:123–138PubMedCrossRefGoogle Scholar
  8. 8.
    Leonard DM (1997) Ras farnesyltransferase: a new therapeutic target. J Med Chem 40:2971–2990PubMedCrossRefGoogle Scholar
  9. 9.
    Johnston SRD (2001) Farnesyl transferase inhibitors: a novel targeted therapy for cancer. Lancet Oncol 2:18–26PubMedCrossRefGoogle Scholar
  10. 10.
    Bell IM (2004) Inhibitors of farnesyltransferase: a rational approach to cancer chemotherapy? J Med Chem 47:1869–1878PubMedCrossRefGoogle Scholar
  11. 11.
    Le DT, Shannon KM (2002) Ras processing as a therapeutic target in hematologic malignancies. Curr Opin Hematol 9:pp308–315PubMedCrossRefGoogle Scholar
  12. 12.
    Caponigro F, Casale M, Bryce J (2004) Farnesyl transferase inhibitors in clinical development. Expert Opin Investig Drugs 12:943–954CrossRefGoogle Scholar
  13. 13.
    Santucci R, Mackley PA, Sebti S, Alsina M (2003) Farnesyltransferase inhibitors and their role in the treatment of multiple myeloma. Cancer Control 10:384–387PubMedGoogle Scholar
  14. 14.
    Rao S, Cunningham D, de Gramont A et al (2004) Phase III double-blind placebo-controlled study of farnesyl transferase inhibitor r115777 in patients with refractory advanced colorectal cancer. J Clin Oncol 22:3950–3957PubMedCrossRefGoogle Scholar
  15. 15.
    Lobell RB, Liu D, Buser CA et al (2002) Preclinical and clinical pharmacodynamic assessment of L-778,123, a dual inhibitor of farnesyl:protein transferase and geranylgeranyl:protein transferase type-I. Mol Cancer Ther 1:747–758PubMedGoogle Scholar
  16. 16.
    Khuri FR, Glisson BS, Kim ES et al (2004) Phase I study of the farnesyltransferase inhibitor lonafarnib with paclitaxel in solid tumors. Clin Cancer Res 10:2968–2976PubMedCrossRefGoogle Scholar
  17. 17.
    Reid TS, Beese LS (2004) Crystal structures of the anti-cancer clinical candidates R115777 (Zarbestra®/tipifarnib) and BMS-214662 complexed with protein farnesyltransferase suggest mechanism of FTI selectivity. Biochemistry 43:6877–6884PubMedCrossRefGoogle Scholar
  18. 18.
    Adams J (2004) The proteasome: a suitable antineoplastic target. Nat Rev Cancer 4:349–360PubMedCrossRefGoogle Scholar
  19. 19.
    Myung J, Kim KB, Crews CM (2001) Proteasome inhibition: mechanism and inhibitors. Med Res Rev 21:245–273PubMedCrossRefGoogle Scholar
  20. 20.
    Garcá-Echeverría C (2002) Recent advances in the identification and development of 20S proteasome inhibitors. Mini-Rev Med Chem 2:247–259CrossRefGoogle Scholar
  21. 21.
    Boccadoro M, Morgan G, Cavenagh J (2005) Preclinical evaluation of the proteasome inhibitor bortezomib in cancer therapy. Cancer Cell Int 5:18–26PubMedCrossRefGoogle Scholar
  22. 22.
    Paramore A, Frantz S (2003) Bortezomib. Nat Rev Drug Discov 2:611–612PubMedCrossRefGoogle Scholar
  23. 23.
    Adams J, Behnke M, Chen S et al (1998) Potent and selective inhibitors of the proteasome: dipeptidyl boronic acids. Bioorg Med Chem Lett 8:333–338PubMedCrossRefGoogle Scholar
  24. 24.
    Groll M, Kim KB, Kairies N et al (2000) Crystal structure of epoxomicin: 20S proteasome reveals a molecular basis for selectivity of α′,β′-epoxyketone proteasome inhibitors. J Am Chem Soc 122:1237–1238CrossRefGoogle Scholar
  25. 25.
    Gourley M, Williamson JS (2000) Angiogenesis: new targets for the development of anticancer chemotherapies. Curr Pharm Design 6:417–439CrossRefGoogle Scholar
  26. 26.
    Dhanabal M, Jeffers M, LaRochelle WJ (2005) Anti-angiogenic therapy as a cancer treatment paradigm. Curr Med Chem Anti-Canc Agents 5:115–130CrossRefGoogle Scholar
  27. 27.
    Rao BG (2005) Recent developments in the design of specific matrix metalloproteinase inhibitors aided by structural and computational studies. Curr Pharm Design 11:295–322CrossRefGoogle Scholar
  28. 28.
    Borkakoti N (2004) Matrix metalloprotease inhibitors: design from structure. Biochem Soc Trans 32:17–20PubMedCrossRefGoogle Scholar
  29. 29.
    Cross JB, Duca JS, Kaminski JJ, Madison VS (2002) The active site of a zinc-dependent metalloproteinase influences the computed pKa of ligands coordinated to the catalytic zinc ion. J Am Chem Soc 124:11004–11007PubMedCrossRefGoogle Scholar
  30. 30.
    Coussens LM, Fingleton B, Matrisian LM (2002) Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 295:2387–2392PubMedCrossRefGoogle Scholar
  31. 31.
    Bissett D, O’Byrne KJ, von Pawel J et al (2005) Phase III study of matrix metalloproteinase inhibitor prinomastat in non-small-cell lung cancer. J Clin Oncol 23:842–849PubMedCrossRefGoogle Scholar

Copyright information

© Feseo 2007

Authors and Affiliations

  1. 1.Departamento de Química Orgánica y FarmacéuticaUniversidad ComplutenseMadridSpain

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