Skip to main content
SpringerLink
Log in

Ras-Farnesyltransferase-Inhibitors as Promising Anti-Tumor Drugs

  • Chapter
  • First Online:
Bioorganic Chemistry of Biological Signal Transduction

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 211))

Abstract

The protein Ras, an important intracellular signal transducer, is crucially involved in the development of tumor growth. The farnesylation of Ras, catalyzed by the enzyme Ras-farnesyltransferase, is essential to its proper functioning in the normal and in the transformed state. Therefore, the inhibition of Ras lipidation has become a promising target for the development of new classes of anti-tumor agents. This review focuses on the different classes of Ras-farnesyltransferase inhibitors and compares their biological properties and modes of action in vitro as well as in vivo.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 16.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

8 References

  1. (a) Barbacid M (1987) Ann Rev Biochem 56:779; (b) Lodish H, Baltimore D, Berk A, Zipursky SL, Matsudeira P, Darnell J (1995) Molecular Cell Biology, 3rd edn. Freeman, New York, Chap 20; (c) Hinterding K, Alonso-Díaz D, Waldmann H (1998) Angew Chem Int Ed 37:688

    Article  CAS  Google Scholar 

  2. (a) Levitzki A (1994) Eur J Biochem 226:1; (b) Pai AF, Krengel U, Goody RS, Kabsch W, Wittinghofer A (1990) EMBO J 9:2351

    Article  CAS  Google Scholar 

  3. Buolamwini KJ (1999) Curr Op Chem Biol 3:500

    Article  CAS  Google Scholar 

  4. Waddick KG, Uckun FM (1998) Biochem Pharmacol 56:1411

    Article  CAS  Google Scholar 

  5. Hancock JF, Paterson H, Marshall CJ (1990) Cell 63:133

    Article  CAS  Google Scholar 

  6. Dudler T, Gelb MH (1996) J Biol Chem 271:11, 541

    Article  Google Scholar 

  7. Moomaw JF, Casey PJ, (1992) J Biol Chem 267:17, 438

    Google Scholar 

  8. Reiss Y, Brown MS, Goldstein JL (1992) J Biol Chem 267:6403

    CAS  Google Scholar 

  9. Cox AD, Der CJ (1997) Biochim Biophys Acta 1333:F51

    CAS  Google Scholar 

  10. Leonard DM (1997) J Med Chem 40:2971

    Article  CAS  Google Scholar 

  11. Buss JE, Marsters JC Jr (1995) Chem Biol 2:787

    Article  CAS  Google Scholar 

  12. Gibbs JB, Graham SL, Hartmann GD, Voblau KS, Vohl NE, Omer CA, Oliff A (1997) Curr Op Chem Biol 1:197

    Article  CAS  Google Scholar 

  13. Stradley SJ, Rizo J, Gierasch LM (1993) Biochemistry 32:12, 586

    Article  Google Scholar 

  14. Koblan KS, Bogusky MJ (1995) Protein Sci 4:681

    Article  CAS  Google Scholar 

  15. Park HW, Boduhire SR, Momaw JF, Casey PJ, Beese LS (1997) Science 275:1800

    Article  CAS  Google Scholar 

  16. Long SB, Casey PJ, Beese LS (1998) Biochemistry 37:9612

    Article  CAS  Google Scholar 

  17. Long SB, Casey PJ, Beese LS (2000) Structure 8:209

    Article  CAS  Google Scholar 

  18. Vohl NE, Wilson FR, Mosser SD, Guiliani E, Solms SJ, Conner MW, Anthony NJ, Holtz WJ, Gomez RP, Lee TJ, Smith RL, Graham SL, Hartman GD, Gibbs JB, Oliff A (1994) Proc Natl Acad Sci 91:9141

    Article  Google Scholar 

  19. Prendergast GC, Davide JP, de Solms SJ, Giuliani E, Graham SL, Gibbs JB, Oliff A, Vohl NE (1994) Mol Cell Biol 14:4193

    CAS  Google Scholar 

  20. Adamson P, Marshall JC, Hall A, Tilbook PA (1992) J Biol Chem 267:20, 033

    Google Scholar 

  21. Du W, Lebowitz PF, Prendergast GC (1999) Mol Cell Biol 19:1831

    CAS  Google Scholar 

  22. Lebovitz PF, Davide JP, Prendergast GC (1995) Mol Cell Biol 15:6613

    Google Scholar 

  23. Nagasu T, Yoshimatsu K, Rowell C, Lewis MD, Garcia AM (1995) Cancer Res 55:5310

    CAS  Google Scholar 

  24. Leftheris K, Kline T, Vite GD, Cho YH, Bhide RS, Patel DV, Manorama M, Schmidt RJ, Weller HN (1996) J Med Chem 39:224

    Article  CAS  Google Scholar 

  25. Hunt JT, Lee VG, Leftheris K, Seizinger B, Carboni J, Mabus J, Ricca C, Yan N, Manne V (1996) J Med Chem 39:353

    Article  CAS  Google Scholar 

  26. James GL, Goldstein JL, Brown MS, Rawson TE, Somers TC, McDowell RS, Crowley CW, Lucas BK, Levinson AD, Marsters JC Jr (1993) Science 260:1937

    Article  CAS  Google Scholar 

  27. James GL, Brown MS, Cobb MH, Goldstein JL (1994) J Biol Chem 269:27, 705

    Google Scholar 

  28. Nigam M, Seong C-M, Qion Y, Hamilton AD, Sebti SM (1993) J Biol Chem 268:20, 695

    Google Scholar 

  29. Qian Y, Blaskovitch MA, Sahem M, Seong CM, Wathen SP, Hamilton AD, Sebti SM (1994) J Biol Chem 269:12, 410

    Google Scholar 

  30. Lerner EC, Qian Y, Blaskovitch MA, Fossum RD, Vogt A, Sun J, Cox AD, Der CJ, Hamilton AD, Sebti SM (1995) J Biol Chem 270:26, 802

    Google Scholar 

  31. Sun J, Qian Y, Blaskovitch MA, Hamilton AD (1995) Cancer Res 55:4243

    CAS  Google Scholar 

  32. Qian Y, Vogt A, Sebti SM, Hamilton AD (1996) J Med Chem 39:217

    Article  CAS  Google Scholar 

  33. Williams TM, Ciccarone TM, MacTough SC, Bock RL, Conner MW, Davide JP, Hamilton K, Koblan KS, Kohl NE (1996) J Med Chem 39:1345

    Article  CAS  Google Scholar 

  34. (a) Patel DV, Gordon EM, Schmidt RJ, Weller HN, Young MG, Zahler R, Barbacid M, Carboni JM, Gullo-Brown JL, Hunikan L, Ricca C, Robinson S, Seizinger BR, Tuormari AV, Manne V (1995) J Med Chem 38:435; (b) Manne V, Yan N, Carboni JM, Tuomari AV, Ricca C, Gullo-Brown J, Andahazy ML, Schmidt RJ, Patel D, Zahler R, Weinmann R, Der CJ, Cox AD, Hunt JT, Gordon EM, Barbacid M, Seizinger BR (1995) Oncogene 10:1763

    Article  CAS  Google Scholar 

  35. Yan N, Ricca C, Fletcher J, Glover T, Seizinger BR, Manne V (1995) Cancer Res 55:3569

    CAS  Google Scholar 

  36. Schlitzer M, Sattler J (1999) Angew Chem Int Ed 38:2032

    Article  CAS  Google Scholar 

  37. (a) Hinterding K, Hagenbuch P, Rétey J, Waldmann H (1998) Angew Chem Int Ed 37:1236; (b) Hinterding K, Hagenbuch P, Rétey J, Waldmann H (1999) Chem Eur J 5:227

    Article  CAS  Google Scholar 

  38. Hara M, Akasaya K, Akinaya S, Ohabe M, Nakano H, Gomez R, Wood D, Uh M, Tamanoi F (1993) Proc Natl Acad Sci 90:2281

    Article  CAS  Google Scholar 

  39. Singh SB, Jones ET, Goetz MA, Bills GF, Nallin-Omstead M, Jenkins RG, Kingham RB, Silverman KC, Gibbs JB (1994) Tetrahedron Lett 35:4963

    Article  Google Scholar 

  40. Singh SB, Zink DL, Liesch JM, Ball RG, Goetz MA, Bolessa EA, Giacobbe RA, Silverman KC, Bills GF (1994) J Org Chem 59:6269

    Google Scholar 

  41. Leonard DM, Schuber KR, Poulter CJ, Eaton SR, Sawyer TK, Hodges JC, Su T-Z, Scholten JD, Gowan R, Sebold-Leopold JS, Doherty AM (1997) J Med Chem 40:192

    Article  CAS  Google Scholar 

  42. Rawls RL (1998) Chem Eng News 67

    Google Scholar 

  43. Mallams AK, Njoroge FG, Doll RJ, Snow ME, Kaminski JJ, Rossmann RR, Vibulbhan B, Bishop WR, Kirschmeier P, Carruthers NI, Wong JK (1997) Bioorg Med Chem 5:93

    Article  CAS  Google Scholar 

  44. Njoroge FG, Doll RJ, Vibulbhan B, Alvarez CS, Bishop WR, Petrin J, Kirschmeier P, Carruthers NI, Wong JK (1997) Bioorg Med Chem 5:101

    Article  CAS  Google Scholar 

  45. Kohl NE, Omer CA, Conner MW, Anthony NJ, Davide JP, deSolms SJ, Guiliani EA, Gomez RP, Graham SL (1995) Nature Medicine 1:792

    Article  CAS  Google Scholar 

  46. Graham SM, Vojtek AB, Huff SY, Cox AC, Clark J, Woper JA, Der CJ (1996) Mol Cell Biol 16:6132

    CAS  Google Scholar 

  47. Finney RE, Bishop JM (1993) Science 260:1524

    Article  CAS  Google Scholar 

  48. James GL, Goldstein JL, Brown MS (1996) Proc Antl Acad Sci USA 93:4454

    Article  CAS  Google Scholar 

  49. Lavell F (1997) CR Seances Soc Biol Fil 191:211

    Google Scholar 

  50. Zhang FL, Kirschmeier CD, James L, Bond RW, Wang L, Patton R, Windsor WT, Syto R, Zhang RM, Bishop WR (1997) J Bio Chem 272:10, 232

    Google Scholar 

  51. Whyte DB, Kirschmeier P, Hockenberry NN, Nunez-Olivia I, Catino JJ, Bishop WR, Pai J-K (1997) J Biol Chem 272:14, 459

    Article  Google Scholar 

  52. Powell CA, Kowalczyk JJ, Lewis MD, Garcia AM (1997) J Biol Chem 272:14, 093

    Google Scholar 

  53. Lebowitz PF, Davide JP, Prendergast GC (1995) Mod Cell Biol 10:2289

    Google Scholar 

  54. Lebowitz PF, Casey PJ, Prendergast GC, Thiessen JA (1997) J Biol Chem 272:15, 591

    Google Scholar 

  55. Clark GJ, Knich MS, Rogers-Graham K, Sebti SM, Hamilton AD, Der CJ (1997) J Biol Chem 272:10, 608

    Google Scholar 

  56. Lebowitz PF, Sakamuro D, Prendergast GC (1997) Cancer Res 57:708

    CAS  Google Scholar 

  57. Lovell RB, Kohl NE (1998) Cancer Metastasis Rev 17:203

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Max-Planck-Institut für molekulare Physiologie, Otto-Hahn-Strasse 11, 44227, Dortmund, Germany

    Herbert Waldmann & Michael Thutewohl

  2. Fb. 3, Organische Chemie, Universität Dortmund, Otto-Hahn-Strasse 6, 44227, Dortmund, Germany

    Herbert Waldmann & Michael Thutewohl

Authors
  1. Herbert Waldmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Thutewohl
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Max-Planck-Institut für Molekulare Physiologie, Universität Dortmund, Otto-Hahn-Straße 11, 44221, Dortmund, Germany

    Herbert Waldmann

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Waldmann, H., Thutewohl, M. (2000). Ras-Farnesyltransferase-Inhibitors as Promising Anti-Tumor Drugs. In: Waldmann, H. (eds) Bioorganic Chemistry of Biological Signal Transduction. Topics in Current Chemistry, vol 211. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-45035-1_4

Download citation

  • DOI: https://doi.org/10.1007/3-540-45035-1_4

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-67746-8

  • Online ISBN: 978-3-540-45035-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation