Farnesyltransferase inhibitors. Preclinical development

Annals of the New York Academy of Sciences

Volumn 886, Issue , 1999, Pages 91-102

  Kohl, Nancy E ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 [[2 [[2 [(2 AMINO 3 MERCAPTOPROPYL)AMINO] 3 METHYLPENTYL]OXY] 1 OXO 3 PHENYLPROPYL]AMINO] 4 (METHYLSULFONYL)BUTANOIC ACID ISOPROPYL ESTER; ANTINEOPLASTIC AGENT; BENZYLOXYCARBONYLHISTIDYL(O BENZYLTYROSYL)(O BENZYLSERYL)TRYPTOPHYL DEXTRO ALANINAMIDE; BMS 186511; BZA 28; BZA 58; GUANINE NUCLEOTIDE BINDING PROTEIN; L 704272; L 745631; MEMBRANE PROTEIN; N (8 AMINO 2 BENZYL 5 ISOPROPYL 9 MERCAPTO 3,6 NONADIENOYL)METHIONINE; N (8 AMINO 2 BENZYL 5 ISOPROPYL 9 MERCAPTO 3,6 NONADIENOYL)METHIONINE METHYL ESTER; N [2 [2 (2 AMINO 3 MERCAPTOPROPYLAMINO) 3 METHYLPENTYLOXY] 3 PHENYLPROPIONYL]METHIONINE SULFONE; N [2 [2 (2 AMINO 3 MERCAPTOPROPYLAMINO) 3 METHYLPENTYLOXY] 3 PHENYLPROPIONYL]METHIONINE SULFONE METHYL ESTER; N [[5 [(2 AMINO 3 MERCAPTOPROPYL)AMINO][1,1' BIPHENYL] 2 YL]CARBONYL]METHIONINE; N [[5 [(2 AMINO 3 MERCAPTOPROPYL)AMINO][1,1' BIPHENYL] 2 YL]CARBONYL]METHIONINE METHYL ESTER; PROTEIN FARNESYLTRANSFERASE; PROTEIN FARNESYLTRANSFERASE INHIBITOR; RAS PROTEIN; SCH 54429; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; BREAST TUMOR; CELL TRANSFORMATION; CONFERENCE PAPER; FIBROBLAST; NONHUMAN; PROTEIN LOCALIZATION; SALIVARY GLAND TUMOR; TRANSGENIC MOUSE;

MAMMALIA; MUS MUSCULUS; OXY;

EID: 0033427141     PISSN: 00778923     EISSN: None     Source Type: Book Series    
DOI: 10.1111/j.1749-6632.1999.tb09404.x     Document Type: Conference Paper

References (70)

1. 1. Barbacid, M. 1987. ras Genes. Ann. Rev. Biochem. 56: 779-827.
2. 2. Bos, J.L. 1988. The ras gene family and human carcinogenesis. Mutation Res. 195: 255-271.
3. 3. Bos, J.L. 1989. ras oncogenes in human cancer: A review. Cancer Res. 49: 4682-4689.
4. 4. Zhang, F.L. & P.J. Casey. 1996. Protein prenylation: Molecular mechanisms and functional consequences. Ann. Rev. Biochem. 65: 241-269.
5. 5. Willumsen, B.M., K. Norris, A.G. Papageorge, N.L. Hubbert & D.R. Lowy. 1984. Harvey murine sarcoma virus p21 ras protein: Biological and biochemical significance of the cysteine nearest the carboxy terminus. EMBO J. 3: 2581-2585.
6. 6. Kato, K., A.D. Cox, M.M. Hisaka, S.M. Graham, J.E. Buss & C.J. Der. 1992. Isoprenoid addition to Ras protein is the critical modification for its membrane association and transforming activity. Proc. Natl. Acad. Sci. USA 89: 6403-6407.
7. 7. Jackson, J.H., C.G. Cochrane, J.R. Bourne, P.A. Solski, J.E. Buss & C.J. Der. 1990. Farnesol modification of Kirsten-ras exon 4B protein is essential for transformation. Proc. Natl. Acad. Sci. USA 87: 3042-3046.
8. 8. Hancock, J.F., A.I. Magee, J.E. Childs & C.J. Marshall. 1989. All ras proteins are polyisoprenylated but only some are palmitoylated. Cell 57:1167-1177.
9. 9. Gibbs, J.B. 1991. Ras C-terminal processing enzymes: New drug targets? Cell 65: 1-4.
10. 10. Reiss, Y., M.S. Brown & J.L. Goldstein. 1992. Divalent cation and prenyl pyrophosphate specificities of the protein farnesyltransferase from rat brain, a zinc metalloenzyme. J. Biol. Chem. 267: 6403-6408.
11. 11. Gibbs, J.B. & A. Oliff. 1997. The potential of farnesyltransferase inhibitors as cancer chemotherapeutics. Ann. Rev. Pharmacol. Toxicol. 37: 143-166.
12. 12. Lebowitz, P.F., P.J. Casey, G.C. Prendergast & J.A. Thissen. 1997. Farnesyltransferase inhibitors alter the prenylation and growth-stimulating function of RhoB. J. Biol. Chem. 272: 15591-15594.
13. 13. Moores, S.L., M.D. Schaber, S.D. Mosser, E. Rands, M.B. O'Hara, V.M. Garsky, M.S. Marshall, D.L. Pompliano & J.B. Gibbs. 1991. Sequence dependence of protein isoprenylation. J. Biol. Chem. 266: 14603-14610.
14. 14. James, G., J.L. Goldstein & M.S. Brown. 1996. Resistance of K-RasBV12 proteins to farnesyltransferase inhibitors in Ratl cells. Proc. Natl. Acad. Sci. USA 93: 4454-4458.
15. 15. Zhang, F.L., P. Kirschmeier, D. Carr, L. James, R.W. Bond, L. Wang, R. Patton, W.T. Windsor, R. Syto, R. Zhang & W.R. Bishop. 1997. Characterization of Ha-Ras, N-Ras, Ki-Ras4A, and Ki-Ras4B as in vitro substrates for farnesyl protein transferase and geranylgeranyl protein transferase type I. J. Biol. Chem. 272: 10232-10239.
16. 16. Trueblood, C.E., Y. Ohya & J. Rine. 1993. Genetic evidence for in vivo cross-specificity of the CaaX-box proteinprenyltransferases farnesyltransferase and geranylgeranyltransferase-I in Saccharomyces cerevisiae. Molec. Cell. Biol. 13: 4260-4275.
17. 17. Rowell, C.A., J.J. Kowalczyk, M.D. Lewis & A.M. Garcia. 1997. Direct demonstration of geranylgeranylation and farnesylation of Ki-Ras in vivo. J. Biol. Chem. 272: 14093-14097.
18. 18. Whyte, D.B., P. Kirschmeier, T.N. Hockenberry, I. Nunez-Oliva, L. James, J.J. Catino, W.R. Bishoip & J.-K. Pai. 1997. K-and N-Ras are geranylgeranylated in cells treated with farnesyl protein transferase inhibitors. J. Biol. Chem. 272: 14459-14464.
19. ras farnesyl:protein transferase by Cys-AAX tetrapeptides. Cell 62: 81-88.
20. 20. Schaber, M.D., M.B. O'Hara, V.M. Garsky, S.D. Mosser, J.D. Bergstrom, S.L. Moores, M.S. Marshall, P.A. Friedman, R.A.F. Dixon & J.B. Gibbs. 1990. Polyisoprenylation of Ras in vitro by a farnesyl-protein transferase. J. Biol. Chem. 265: 14701-14704.
21. 21. Pompliano, D.L., E. Rands, M.D. Schaber, S.D. Mosser, N.J. Anthony & J.B. Gibbs. 1992. Steady-state kinetic mechanism of ras farnesyl:protein transferase. Biochemistry 31: 3800-3807.
22. 22. Goldstein, J.L., M.S. Brown, S.J. Stradley, Y. Reiss & L.M. Gierasch. 1991. Nonfarnesylated tetrapeptide inhibitors of protein farnesyltransferase. J. Biol. Chem. 266: 15575-15578.
23. 23. Kohl, N.E., S.D. Mosser, S.J. DeSolms, E.A. Giuliani, D.L. Pompliano, S.L. Graham, R.L. Smith, E.M. Scolnick, A. Oliff & J.B. Gibbs. 1993. Selective inhibition of ras-dependent transformation by a farnesyltransferase inhibitor. Science 260: 1934-1937.
24. 24. Garcia, A.M., C. Rowell, K. Ackermann, J.J. Kowalczyk & M.D. Lewis. 1993. Peptidomimetic inhibitors of ras farnesylation and function in whole cells. J. Biol. Chem. 268: 18415-18418.
25. 25. Graham, S.L., S.J. DeSolms, E.A. Giuliani, N.E. Kohl, S.D. Mosser, A.I. Oliff, D.L. Pompliano, E. Rands, M.J. Breslin, A.A. Deana, V.M. Garsky, T.H. Scholz, J.B. Gibbs & R.L. Smith. 1994. Pseudopeptide inhibitors of Ras farnesyl-protein transferase. J. Med. Chem. 37: 725-732.
26. 26. Wai, J.S., D.L. Bamberger, T.E. Fisher, S.L. Graham, R.L. Smith, J.B. Gibbs, S.D. Mosser, A.I. Oliff, D.L. Pompliano, E. Rands & N.E. Kohl. 1994. Synthesis and biological activity of Ras farnesyl protein transferase inhibitors. Tetrapeptide analogs with amino methyl and carbon linkages. Bioorg. & Med. Chem. 2: 939-947.
27. 27. Nagasu, T., K. Yoshimatsu, C. Rowell, M.D. Lewis & A.M. Garcia. 1995. Inhibition of human tumor xenograft growth by treatment with the farnesyl transferase inhibitor B956. Cancer Res. 55: 5310-5314.
28. 28. Kohl, N.E., F.R. Wilson, S.D. Mosser, E.A. Giuliani, S.J. DeSolms, M.W. Conner, N.J. Anthony, W.J. Holtz, R.P. Gomez, T.-J. Lee, R.L. Smith, S.L. Graham, G.D. Hartmen, J.B. Gibbs & A. Oliff. 1994. Farnesyltransferase inhibitors block the growth of ras-dependent tumors in nude mice. Proc. Natl. Acad. Sci. USA 91: 9141-9145.
29. 29. DeSolms, S.J., A.A. Deana, E.A. Giuliani, S.L. Graham, N.E. Kohl, S.D. Mosser, A.I. Oliff, D.L. Pompliano, E. Rands, T.H. Scholz, J.M. Wiggins, J.B. Gibbs & R.L. Smith. 1995. Pseudodipeptide inhibitors of protein farnesyltransferase. J. Med. Chem. 38: 3967-3971.
30. 30. Williams, T.M., T.M. Ciccarone, S.C. MacTough, R.L. Bock, M.W. Conner, J.P. Davide, K. Hamilton, K.S. Koblan, N.E. Kohl, A.M. Kral, S.D. Mosser, C.A. Omer, D.L. Pompliano, E. Rands, M.D. Schaber, D. Shah, F.R. Wilson, J.B. Gibbs, S.L. Graham, G.D. Hartman, A.I. Oliff & R.L. Smith. 1996. 2-Substituted piperazines as constrained amino acids. Application to the synthesis of potent, non carboxylic acid inhibitors of farnesyltransferase. J. Med. Chem. 39: 1345-1348.
31. 31. Sebti, S.M. & A.D. Hamilton. 1996. Rational design of Ras prenyltransferase inhibitors as potential anticancer drugs. Biochem. Soc. Trans. 24: 692-699.
32. 32. James, G.L., J.L. Goldstein, M.S. Brown, T.E. Rawson, T.C. Somers, R.S. McDowell, C.W. Crowley, B.K. Lucas, A.D. Levinson & J.J.C. Marsters. 1993. Benzodiazepine peptidomimetics: potent inhibitors of Ras farnesylation in animal cells. Science 260: 1937-1942.
33. 33. Hunt, J.T., V.G. Lee, K. Leftheris, B. Seizinger, J. Carboni, J. Mabus, C. Ricca, N. Yan & V. Manne. 1996. Potent, cell active, non-thiol tetrapeptide inhibitors of farnesyltransferase. J. Med. Chem. 39: 353-358.
34. 34. Bishop, W.R., R. Bond, J. Petrin, L. Wang, R. Patton, R. Doll, G. Njoroge, J. Catino, J. Schwartz, W. Windsor, R. Syto, J. Schwartz, D. Carr, L. James & P. Kirschmeier. 1995. Novel tricyclic inhibitors of farnesyl protein transferase. J. Biol. Chem. 270: 30611-30618.
35. 35. Njoroge, F.G., B. Vibulbhan, C.S. Alvarez, W.R. Bishop, J. Petrin, R.J. Doll, V. Girijavallabhan & A.K. Ganguly. 1996. Novel tricyclic animoacetyl and sulfonamide inhibitors of Ras farnesyl protein transferase. Bioorg Med. Chem. Lett. 6: 2977-2982.
36. 36. Mallams, A.K., F.G. Njoroge, R.J. Doll, M.E. Snow, J.J. Kaminski, R.R. Rossman, B. Vibulbhan, W.R. Bishop, P. Kirschmeier, M. Liu, M.S. Bryant, C. Alvarez, D. Carr, L. James, I. King, Z. Li, C.-C. Lin, C. Nardo, J. Petrin, S.W. Remiszewski, A.G. Taveras, S. Wang, J. Wong, J. Catino, V. Girijavallabhan & A.K. Ganguly. 1997. Antitumor 8-chlorobenzocycloheptapyridines: A new class of selective, nonpeptidic, nonsulfhydryl inhibitors of Ras farnesylation. Bioorg. Med. Chem. 5: 93-99.
37. 37. Njoroge, F.G., R.J. Doll, B. Vibulbhan, C.S. Alvarez, W.R. Bishop, J. Petrin, P. Kirschmeier, N.I. Carruthers, J.K. Wong, M.M. Albanese, J.J. Piwinski, J. Catino, V. Girijavallabhan & A.K. Ganguly. 1997. Discovery of novel nonpeptide tricyclic inhibitors of Ras farnesyl protein transferase. Bioorg. Med. Chem. 5: 101-113.
38. 38. Patel, D.V., R.J. Schmidt, S.A. Biller, E.M. Gordon, S.S. Robinson & V. Manne. 1995. Farnesyl diphosphate-based inhibitors of Ras farnesyl protein transferase. J. Med. Chem. 38: 2906-2921.
39. 39. Manne, V., C.S. Ricca, J.G. Brown, A.V. Tuomari, N. Yan, D. Patel, R. Schmidt, M.J. Lynch, C.P. Ciosek, Jr., J.M. Carboni, S. Robinson, E.M. Gordon, M. Barbacid, B.R. Seizinger & S.A. Biller. 1995. Ras farnesylation as a target for novel antitumor agents: potent and selective farnesyl diphosphate analog inhibitors of farnesyltransferase. Drug Dev. Res. 34: 121-137.
40. 40. Overhand, M., E. Pieterman, L.H. Cohen, A.R.P.M. Valentijn, G.A. Van Der Marel & J.H. Van Boom. 1997. Synthesis of triphosphonate analogues of farnesyl pyrophosphate. Inhibitors of squalene synthase and protein:farnesyl transferase. Bioorg. & Med. Chem. Lett. 7: 2435-2440.
41. 41. Aoyama, T., T. Satoh, M. Yonemoto, J. Shibata, K. Nonoshita, S. Arai, K. kawakami, Y. Iwasawa, H. Sano, K. Tanaka, Y. Monden, T. Kodera, H. Arakawa, I. Suzuki-Takahashi, T. Kamei & K. Tomimoto. 1998. A new class of highly potent farnesyl diphosphate-competitive inhibitors of farnesyltransferase. J. Med. Chem. 41: 143-147.
42. 42. Yonemoto, M., T. Satoh, H. Arakawa, I. Suzuki-Takahashi, Y. Monden, T. Kodera, K. Tanaka, T. Aoyama, Y. Iwasawa, T. Kamei, S. Nishimura & K. Tomimoto. 1998. J-104,871, a novel farnesyltransferase inhibitor, blocks Ras farnesylation in vivo in a farnesyl pyrophosphate-competitive manner. Molec. Pharmacol. 54: 1-7.
43. 43. Dufresne, C., K.E. Wilson, S.B. Singh, D.L. Zink, J.D. Bergstrom, D. Rew, J.D. Polishook, M. Meinz, L. Huang, K.C. Silverman & R.B. Lingham. 1993. Zaragozic acids D and D2: Potent inhibitors of squalene synthase and of ras farnesyl-protein transferase. J. Natural Prod. 56: 1923-1929.
44. 44. Gibbs, J.B., D.L. Pompliano, S.D. Mosser, E. Rands, R.B. Lingham, S.B. Singh, E.M. Scolnick, N.E. Kohl & A. Oliff. 1993. Selective inhibition of farnesyl-protein transferase blocks ras processing in vivo. J. Biol. Chem. 268: 7617-7620.
45. 45. Kara, M., K. Akasaka, S. Akinaga, M. Okabe, H. Nakano, R. Gomez, D. Wood, M. Uh & F. Tamanoi. 1993. Identification of Ras farnesyltransferase inhibitors by microbial screening. Proc. Natl. Acad. Sci. USA 90: 2281-2285.
46. 46. Lingham, R.B., K.C. Silverman, G.F. Bills, C. Cascales, M. Sanchez, R. G. Jenkins, S. E. Gartner, I. Martin, M. T. Diez, F. Pelaez, S. Mochales, Y.-L. Kong, R. W. Burg, M. S. Meinz, L. Huang, M. Nallin-Omstead, S. D. Mosser, M. D. Schaber, C. A. Omer, D.L. Pompliano, J. B. Gibbs & S.B. Singh. 1993. Chaetomella acutiseta produces chaetomellic acids A and B which are reversible inhibitors of farnesyl-protein transferase. Applied Microbiol. & Biotechnol. 40: 370-374.
47. 47. Singh, S.B., D.L. Zink, J.M. Liesch, M.A. Goetz, R.G. Jenkins, M. Nallin-Omstead, K.C. Silverman, G.F. Bills, R.T. Mosley, J.B. Gibbs, G. Albers-Schonberg & R.B. Lingham. 1993. Isolation and structure of chaetomellic acids A and B from Chaetomella acutiseta: farnesyl pyrophosphate mimic inhibitors of Ras farnesyl-protein transferase. Tetrahedron 49: 5917-5926.
48. 48. Singh, S.B., J.M. Liesch, R.B. Lingham, M.A. Goetz & J.B. Gibbs. 1994. Actinoplanic acid A: A macrocyclic polycarboxylic acid which is a potent inhibitor of Ras farnesyl-protein transferase. J. Am. Chem. Soc. 116: 11606-11607.
49. 49. Singh, S.B., J.M. Liesch, R.B. Lingham, K.C. Silverman, J.M. Sigmund & M.A. Goetz. 1995. Structure, chemistry, and biology of actinoplanic acids: Potent inhibitors of Ras farnesyl-protein transferase. J. Organ. Chem. 60: 7896-7901.
50. 50. Van Der Pyl, D., P. Cans, J.J. Debernard, F. Herman, Y. Lelievre, L. Tahraoui, M. Vuilhorgne & J. Leboul. 1995. RPR113228, a novel farnesyl-protein transferase inhibitor produced by Chrysosporium lobatum. J. Antibiotics 736-737.
51. 51. Jayasuriya, H., G.F. Bills, C. Cascales, D.L. Zink, M.A. Goetz, R.G. Jenkins, K.C. Silverman, R.B. Lingham & S.B. Singh. 1996. Oreganic acid: A potent novel inhibitor of Ras farnesyl-protein transferase from an endophytic fungus. Bioorg. Med. Chem. Lett. 6: 2081-2084.
52. 52. Silverman, K.C., H. Jayasuriya, C. Cascales, D. Vilella, G.F. Bills, R.G. Jenkins, S.B. Singh & R.B. Lingham. 1997. Oreganic acid, a potent inhibitor of Ras farnesyl-protein transferase. Biochem. Biophys. Res. Commun. 232: 478-481.
53. 53. Wallace, A., K.S. Koblan, K. Hamilton, D.J. Marquis-Omer, P.J. Miller, S.D. Mosser, C.A. Omer, M.D. Schaber, R. Cortese, A. Oliff, J.B. Gibbs & A. Pessi. 1996. Selection of potent inhibitors of farnesyl-protein transferase from a synthetic tetrapeptide combinatorial library. J. Biol. Chem. 271: 31306-31311.
54. 54. Leonard, D.M., K.R. Shuler, C.J. Poulter, S.R. Eaton, T.K. Sawyer, J.C. Hodges, T.-Z. Su, J.D. Scholten, R.C. Gowan, J.S. Sebolt-Leopold & A.M. Doherty. 1997. Structure-activity relationships of cysteine-lacking pentapeptide derivatives that inhibit ras farnesyltransferase. J. Med. Chem. 40: 192-200.
55. 55. Bhide, R.S., D.V. Patel, M.M. Patel, S.P. Robinson, L.W. Hunihan & E.M. Gordon. 1994. Rational design of potent carboxylic acid based bisubstrate inhibitors of ras farnesyl protein transferase. Bioorg. & Med. Chem. Letts. 4: 2107-2112.
56. 56. Patel, D.V., E.M. Gordon, R.J. Schmidt, H.N. Weller, M.G. Young, R. Zahler, M. Barbacid, J.M. Carboni, J.L. Gullo-Brown, L. Hunihan, C. Ricca, S. Robinson, B.R. Seizinger, A.V. Tuomari & V. Manne. 1995. Phosphinyl Acid-based Bisubstrate Analog Inhibitors Of Ras Farnesyl Protein Transferase. J. Med. Chem. 38: 435-442.
57. 57. Patel, D.V., M.G. Young, S.P. Robinson, L. Hunihan, B.J. Dean & E.M. Gordon. 1996. Hydroxamic acid-based bisubstrate analog inhibitors of Ras farnesyl protein transferase. J. Med. Chem. 39: 4197-4210.
58. 58. Manne, V., N. Yan, J.M. Carboni, A.V. Tuomari, C.S. Ricca, J.G. Brown, M.L. Andahazy, R.J. Schmidt, D. Patel, R. Zahler, R. Weinmann, C.J. Der, A.D. Cox, J.T. Hunt, E.M. Gordon, M. Barbacid & B.R. Seizinger. 1995. Bisubstrate inhibitors of farnesyltransferase: a novel class of specific inhibitors of ras transformed cells. Oncogene 10: 1763-1779.
59. 59. Kohl, N.E., C.A. Omer, M.W. Conner, N.J. Anthony, J.P. Davide, S.J. DeSolms, E.A. Giuliani, R.P. Gomez, S.L. Graham, K. Hamilton, L.K. Handt, G.D. Hartmen, K.S. Koblan, A.M. Kral, P.J. Miller, S.D. Mosser, T.J. O'Neill, E. Rands, M.D. Schaber, J.B. Gibbs & A. Oliff. 1995. Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice. Nature Med. 1: 792-797.
60. 60. Prendergast, G.C., J.P. Davide, S.J. DeSolms, E.A. Giuliani, S.L. Graham, J.B. Gibbs, A. Oliff & N.E. Kohl. 1994. Farnesyltransferase inhibition causes morphological reversion of ras-transformed cells by a complex mechanism that involves regulation of the actin cytoskeleton. Mol. Cell. Biol. 14: 4193-4202.
61. 61. Cox, A.D., A.M. Garcia, J.K. Westwick, J.J. Kowalczyk, M.D. Lewis, D.A. Brenner & C.J. Der. 1994. The CAAX peptidomimetic compound B581 specifically blocks farnesylated, bul not geranylgeranylated or myristylated, oncogenic Ras signaling and transformation. J. Biol. Chem. 269: 19203-19206.
62. 62. Sepp-Lorenzino, L., Z. Ma, E. Rands, N.E. Kohl, J.B. Gibbs, A. Oliff & N. Rosen. 1995. A peptidomimetic inhibitor of farnesyl:protein transferase blocks the anchorage-dependent and -independent growth of human tumor cell lines. Cancer Res. 55: 5302-5309.
63. 63. Cox, A.D., M.M. Hisaka, J.E. Buss & C.J. Der. 1992. Specific isoprenoid modification is required for function of normal, but not oncogenic, ras protein. Mol. Cell. Biol. 12: 2606-2615.
64. 64. Adamson, P., C.J. Marshall, A. Hall & P.A. Tilbrook. 1992. Post-translational modifications of p21rho proteins. J. Biol. Chem. 267: 20033-20038.
65. 65. Sun, J., Y. Qian, A.D. Hamilton & S.M. Sebti. 1995. Ras CAAX peptidomimetic FTI 276 selectively blocks tumor growth in nude mice of a human lung carcinoma with K-ras mutation and p53 deletion. Cancer Res. 55: 4243-4247.
66. 66. Sinn, E., W. Muller, P. Pattengale, I. Tepler, R. Wallace & P. Leder. 1987. Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: Synergistic action of oncogenes in vivo. Cell 49: 465-475.
67. 67. Barrington, R.E., M.A. Subler, E. Rands, C.A. Omer, P.J. Miller, J.E. Hundley, S.K. Koester, D.A. Troyer, D.J. Bearss, M.W. Conner, J.B. Gibbs, K. Hamilton, K.S. Koblan, S.D. Mosser, T.J. O'Neill, M.D. Schaber, E.T. Senderak, J.J. Windle, A. Oliff & N.E. Kohl. 1998. A farnesyltransferase inhibitor induces tumor regression in transgenic mice harboring multiple oncogenic mutations by mediating alterations in both cell cycle control and apoptosis. Mol. Cell. Biol. 18: 85-92.
68. 68. Lebowitz, P.F., D. Sakamur & G.C. Prendergast. 1997. Farnesyl transferase inhibitors induce apoptosis of ras-transformed cells denied substratum attachment. Cancer Res. 57: 708-713.
69. 69. Mangues, R., T. Corral, N.E. Kohl, W.F. Symmans, S. Lu, M. Malumbres, J.B. Gibbs, A. Oliff & A. Pellicer. 1998. Antitumor effect of a farnesyl transferase inhibitor in mammary and lymphoid tumors overexpressing N-ras in transgenic mice. Cancer Res. 58: 1253-1259.
70. 70. James, G.L., M.S. Brown, M.H. Cobb & J.L. Goldstein. 1994. Benzodiazepine peptidomimetic BZA-5B interrupts the MAP kinase activation pathway in H-Ras-transformed Rat-1 cells, but not in untransformed cells. J. Biol. Chem. 269: 27705-27714.