Cancer pp 133-168 | Cite as

Farnesyl Protein Transferase Inhibitors: Medicinal Chemistry, Molecular Mechanisms, and Progress in the Clinic

Part of the Topics in Medicinal Chemistry book series (TMC, volume 1)


Over a decade has passed since the first report describing farnesyl protein transferase (FTase)and tetrapeptide inhibitors triggered a search for small-molecule inhibitors that could be developedas oral therapeutics. There are now several farnesyl protein inhibitors (FTIs) in various phases of clinicaldevelopment and at least two compounds have entered phase III. The published data suggest some disappointingactivity in the major solid tumors, with more promising activities emerging from studies of hematologicalmalignancies and glioblastoma. The current compounds emerged from various research strategies includingmodeling around the CAAX motif peptide substrate and the farnesyl pyrophosphate (FPP) substrate, as wellas high-throughput screening campaigns. The interaction of inhibitors in the active site of the FT enzymecan be accurately described thanks to the publication of the X-ray structure as well as excellent mechanisticwork. Published structure–activity data have revealed an interesting convergence on imidazole pharmacophores.The original hypothesis that drove development of FTIs anticipated therapy targeted specifically at thefarnesylated Ras oncoproteins and cancers with ras gene mutations. Asexperience with the newer potent FTIs grew, data emerged to suggest that multiple downstream effectors contributeto the antitumor activity of FTIs. The mechanism(s) of action of FTIs and the full therapeutic activityof the class remain areas of active investigation.

Farnesyl transferase inhibitor Protein prenylation Ras protein Acute myeloid leukemia 



A-kinase anchoring protein 13


Acute myelogenous leukemia


Centromere-associated protein-E


Centromere-associated protein-F


Central nervous system




Farnesyl pyrophosphate


Farnesyl protein transferase


Farnesyl protein transferase inhibitor


Geranylgeranyl protein transferase


Growth factor receptor binding protein-2β


Guanosine triphosphate




Harvey ras gene


Neural ras gene


Kirsten ras gene


Human DNAJ-2 heat shock protein


Human umbilical vein endothelial cell


Mammalian target of rapamycin


Nuclear factor kappa B deoxyribonucleic acid


Nuclear magnetic resonance


Phosphoinositide-3-kinase/serine–threonine kinase Akt-3


Protein geranylgeranyl transferase


Duration of the QT interval corrected for changes in the heart rate


Rab geranylgeranyl transferase


Ras CAAX endoprotease


Ras homolog enriched in brain


Structure–activity relationship


Sequence homology-2/sequence homology-3


Son of sevenless


Transforming growth factor β




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The authors would like to thank everyone at Johnson & Johnson who has worked on FTIs over the years.


  1. 1.
    Quesney-Huneeus V, Wiley MH, Siperstein MD (1979) Proc Natl Acad Sci USA 76:5056 CrossRefGoogle Scholar
  2. 2.
    Habenicht AJ, Glomset JA, Ross R (1980) J Biol Chem 255:5134 Google Scholar
  3. 3.
    Schmidt RA, Schneider CJ, Glomset JA (1984) J Biol Chem 259:10175 Google Scholar
  4. 4.
    Beck LA, Hosick TJ, Sinensky M (1988) J Cell Biol 107:1307 CrossRefGoogle Scholar
  5. 5.
    Casey PJ, Solski PA, Der CJ, Buss J (1989) Proc Natl Acad Sci USA 86:832 CrossRefGoogle Scholar
  6. 6.
    Leonard S, Beck L, Sinensky M (1990) J Biol Chem 265:5157 Google Scholar
  7. 7.
    Barbacid M (1987) Ann Rev Biochem 56:779 CrossRefGoogle Scholar
  8. 8.
    Kato K, Cox AD, Hisaka MM, Graham SM, Buss JE, Der CJ (1992) Proc Natl Acad Sci USA 89:6403 CrossRefGoogle Scholar
  9. 9.
    Jackson JH, Cochrane CG, Bourne JR, Solski PA, Buss JE, Der CJ (1990) Proc Natl Acad Sci USA 87:3042 CrossRefGoogle Scholar
  10. 10.
    Sinensky M, Beck LA, Leonard S, Evans R (1990) J Biol Chem 265:19937 Google Scholar
  11. 11.
    Gibbs JB (1991) Cell 65:1 CrossRefGoogle Scholar
  12. 12.
    Reiss Y, Goldstein JL, Seabra MC, Casey PJ, Brown MS (1990) Cell 62:81 CrossRefGoogle Scholar
  13. 13.
    Cox AD, Der CJ (1997) Biochim Biophys Acta 1333:F51 Google Scholar
  14. 14.
    Zujewski J, Horak ID, Woestenborghs R, Chiao J, Cusack G, Kohler D, Kremer AB, Cowan KH (1998) Proc Am Assoc Cancer Res 39:270 Google Scholar
  15. 15.
    Hudes GR, Schol J, Baab J, Rogatko A, Bol C, Horak I, Langer C, Goldstein LJ, Szarka C, Meropol NJ, Weiner L (1999) Proc Am Soc Clin Oncol 18:601 Google Scholar
  16. 16.
    Adjei AA, Erlichman C, Davis JN, Reid J, Sloan J, Statkevich P, Zhu Y, Marks RS, Pitot HC, Goldberg R, Hanson L, Alberts S, Cutler D, Kaufman SH (1999) Proc Am Soc Clin Oncol 18:598 Google Scholar
  17. 17.
    Schellens JHM, De Klerk G, Swart M, Palmer PA, Bol CJ, Van't Veer LJ, Tan H, ten Bokkel Huinink WW, Beijnen JH (1999) Proc Am Assoc Cancer Res 40:724 Google Scholar
  18. 18.
    Nakagawa K, Yamamoto N, Nishio K, Ohashi Y, End D, Bol Kees, Ito H, Fukuoka M (2001) Proc Am Soc Clin Oncol 20:317 Google Scholar
  19. 19.
    Raponi M, Belly RT, Karp JE, Lancet JE, Atkind D, Wang Y (2004) BMC Cancer 4:56 CrossRefGoogle Scholar
  20. 20.
    Raponi M, Zhang Y, Jatkoe T, Yu J, Lee G, Lancet JE, Karp JE, Thibault A, Wang X (2005) Blood 106:Abstract 2785 Google Scholar
  21. 21.
    Maltese WA, Erdman RA (1989) J Biol Chem 264:18168 Google Scholar
  22. 22.
    Pompliano DL, Schaber MD, Mosser SD, Omer CA, Shafer JA, Gibbs JB (1993) Biochemistry 32:8341 CrossRefGoogle Scholar
  23. 23.
    Furfine ES, Leban JJ, Landavazo A, Moomaw JF, Casey PJ (1995) Biochemistry 34:6857 CrossRefGoogle Scholar
  24. 24.
    Strickland CL, Windsor WT, Syto R, Wang L, Bond R, Wu Z, Schwartz J, Le HV, Beese LS, Weber PC (1998) Biochemistry 37:16601 CrossRefGoogle Scholar
  25. 25.
    Yokoyama K, McGeady P, Gelb MH (1995) Biochemistry 34:1344 CrossRefGoogle Scholar
  26. 26.
    Park HW, Boduluri SR, Moomaw JF, Casey PJ, Beese LS (1997) Science 275:1800 CrossRefGoogle Scholar
  27. 27.
    Long SB, Casey PJ, Beese LS (1998) Biochemistry 37:9612 CrossRefGoogle Scholar
  28. 28.
    Dunten P, Kammlott U, Crowther R, Weber D, Palermo R, Birktoft J (1998) Biochemistry 37:7907 CrossRefGoogle Scholar
  29. 29.
    Huang CC, Casey PJ, Fierke CA (1997) J Biol Chem 272:20 CrossRefGoogle Scholar
  30. 30.
    Hightower KE, Huang CC, Casey PJ, Fierke CA (1998) Biochemistry 37:15555 CrossRefGoogle Scholar
  31. 31.
    Reiss Y, Seabra MC, Armstrong SA, Slaughter CA, Goldstein JL, Brown MS (1991) J Biol Chem 266:10672 Google Scholar
  32. 32.
    Seabra MC, Reiss Y, Casey PJ, Brown MS, Goldstein JL (1991) Cell 65:429 CrossRefGoogle Scholar
  33. 33.
    Otto JC, Kim E, Young SG, Casey PJ (1999) J Biol Chem 274:8379 CrossRefGoogle Scholar
  34. 34.
    Gutierrez L, Magee AI, Marshall CJ, Hancock JF (1989) EMBO J 8:1093 Google Scholar
  35. 35.
    Seabra MC, Goldstein JL, Sudhof TC, Brown MS (1992) J Biol Chem 267:14497 Google Scholar
  36. 36.
    Seabra MC, Brown MS, Slaughter CA, Sudhof TC, Goldstein JL (1992) Cell 70:1049 CrossRefGoogle Scholar
  37. 37.
    Egan SE, Giddings BW, Brooks MW, Buday L, Sizeland AM, Weinberg RA (1993) Nature 363:45 CrossRefGoogle Scholar
  38. 38.
    Stokoe D, Macdonald SG, Cadwallader K, Symons M, Hancock JF (1994) Science 264:1463 CrossRefGoogle Scholar
  39. 39.
    Moodie SA, Willumsen BM, Weber MJ, Wolfman A (1993) Science 260:1658 CrossRefGoogle Scholar
  40. 40.
    Kohl NE, Mosser SD, deSolms SJ, Giuliani EA, Pompliano DL, Graham SL, Smith RL, Scolnick EM, Oliff A, Gibbs JB (1993) Science 260:1934 CrossRefGoogle Scholar
  41. 41.
    James GL, Goldstein JL, Brown MS, Rawson TE, Somers TC, McDowell RS, Crowley CW, Lucas BK, Levinson AD, Marsters JC (1993) Science 260:1937 CrossRefGoogle Scholar
  42. 42.
    Sepp-Lorenzino L, Ma Z, Rands E, Kohl NE, Gibbs JB, Oliff A, Rosen N (1995) Cancer Res 55:5302 Google Scholar
  43. 43.
    End DW, Smets G, Todd AV, Applegate TL, Fuery CJ, Angibaud P, Venet M, Sanz G, Poignet H, Skrzat S, Devine A, Wouters W, Bowden C (2001) Cancer Res 61:131 Google Scholar
  44. 44.
    James G, Goldstein JL, Brown MS (1996) Proc Natl Acad Sci USA 93:4454 CrossRefGoogle Scholar
  45. 45.
    Rowell CA, Kowalczyk JJ, Lewis MD, Garcia AM (1997) J Biol Chem 272:14093 CrossRefGoogle Scholar
  46. 46.
    Whyte DB, Kirschmeier P, Hockenberry TN, Nunez-Oliva I, James L, Catino JJ, Bishop WR, Pai JK (1997) J Biol Chem 272:14459 CrossRefGoogle Scholar
  47. 47.
    Grunewald K, Lyons J, Frohlich A, Feichtinger H, Weger RA, Schwab G, Janssen JW, Bartram CR (1989) Int J Cancer 43:1037 CrossRefGoogle Scholar
  48. 48.
    Forrester K, Almoguera C, Han K, Grizzle WE, Perucho M (1987) Nature 327:298 CrossRefGoogle Scholar
  49. 49.
    Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL (1988) N Engl J Med 319:525 CrossRefGoogle Scholar
  50. 50.
    Reynolds SH, Anna CK, Brown KC, Wiest JS, Beattie EJ, Pero RW, Iglehart JD, Anderson MW (1991) Proc Natl Acad Sci USA 88:1085 CrossRefGoogle Scholar
  51. 51.
    Knowles MA, Williamson M (1993) Cancer Res 53:133 Google Scholar
  52. 52.
    Nagasu T, Yoshimatsu K, Rowell C, Lewis MD, Garcia AM (1995) Cancer Res 55:5310 Google Scholar
  53. 53.
    Maltese WA (1990) FASEB J 4:3319 Google Scholar
  54. 54.
    Sun J, Qian Y, Hamilton AD, Sebti SM (1998) Oncogene 16:1467 CrossRefGoogle Scholar
  55. 55.
    Lobell R, Anthony N, Bell I, Buser C, Desolms J, Dinsmore C, Gibbs J, Graham S, Hartman G, Heimbrook D, Huber H, Lumma W, William T, Kohl N (2001) Proc Am Assoc Cancer Res 42:259 Google Scholar
  56. 56.
    Prendergast GC (2001) Histol Histopathol 16:269 Google Scholar
  57. 57.
    Hall A (1998) Science 279:509 CrossRefGoogle Scholar
  58. 58.
    Prendergast GC, Khosravi-Far R, Solski PA, Kurzawa H, Lebowitz PF, Der CJ (1995) Oncogene 10:2289 Google Scholar
  59. 59.
    Adamson P, Marshall CJ, Hall A, Tilbrook PA (1992) J Biol Chem 267:20330 Google Scholar
  60. 60.
    Baron R, Fourcade E, Lajoie-Mazenc I, Allal C, Couderc B, Barbaras R, Favre G, Faye JC, Pradines A (2000) Proc Natl Acad Sci USA 97:11626 CrossRefGoogle Scholar
  61. 61.
    Lebowitz PF, Casey PJ, Prendergast GC, Thissen JA (1997) J Biol Chem 272:15591 CrossRefGoogle Scholar
  62. 62.
    Du W, Lebowitz PF, Prendergast GC (1999) Mol Cell Biol 19:1831 Google Scholar
  63. 63.
    Du W, Prendergast GC (1999) Cancer Res 59:5492 Google Scholar
  64. 64.
    Liu AX, Du W, Liu JP, Jessell TM, Prendergast GC (2000) Mol Cell Biol 20:6105 CrossRefGoogle Scholar
  65. 65.
    Liu AX, Cerniglia GJ, Bernhard EJ, Prendergast GC (2001) Proc Natl Acad Sci USA 98:6192 CrossRefGoogle Scholar
  66. 66.
    Teyssier F, Dalenc F, Pradines A, Couderc B, Ader I, Bonnet J, Cohen-Jonathan E, Toulas C, Favre G (2001) Proc Am Assoc Cancer Res 42:489 Google Scholar
  67. 67.
    Van Golen KL, Bao LW, DiVito MM, Wu ZF, Prendergast GC, Merajver SD (2002) Mol Cancer Ther 1:575 Google Scholar
  68. 68.
    Chen Z, Sun J, Pradines A, Favre G, Adnane J, Sebti SM (2000) J Biol Chem 275:17974 CrossRefGoogle Scholar
  69. 69.
    DuHadaway JB, Du W, Donover S, Baker J, Liu A, Sharp DM, Muller AJ, Prendergast GC (2003) Oncogene 22:3578 CrossRefGoogle Scholar
  70. 70.
    Kamasani U, Huang M, DuHadaway JB, Prochownik EV, Donover PS, Prendergast GC (2004) Cancer Res 64:8389 CrossRefGoogle Scholar
  71. 71.
    Wolda SL, Glomset JA (1988) J Biol Chem 263:5997 Google Scholar
  72. 72.
    Holtz D, Tanaka RA, Hartwig J, McKeon F (1989) Cell 59:969 CrossRefGoogle Scholar
  73. 73.
    Beck LA, Hosick TJ, Sinensky M (1990) J Cell Biol 110:1489 CrossRefGoogle Scholar
  74. 74.
    Sinensky M, Fantle K, Dalton M (1994) Cancer Res 54:3229 Google Scholar
  75. 75.
    Dalton MB, Fantle KS, Bechtold HA, DeMaio L, Evans RM, Krystosek A, Sinensky M (1995) Cancer Res 55:3295 Google Scholar
  76. 76.
    Toth JI, Yang SH, Qiao X, Beigneux AP, Gelb MH, Moulson CL, Miner JH, Young SG, Fong LG (2005) Proc Natl Acad Sci USA 102:12873 CrossRefGoogle Scholar
  77. 77.
    Capell BC, Erdos MR, Madigan JP, Fiordalisi JJ, Varga R, Conneely KN, Gordon LB, Der CJ, Cox AD, Collins FS (2005) Proc Natl Acad Sci USA 102:12879 CrossRefGoogle Scholar
  78. 78.
    Glynn MW, Glover TW (2005) Hum Mol Genet 14:2959 CrossRefGoogle Scholar
  79. 79.
    Mallampalli MP, Huyer G, Bendale P, Gelb MH, Michaelis S (2005) Proc Natl Acad Sci USA 102:14416 CrossRefGoogle Scholar
  80. 80.
    Crespo NC, Ohkanda J, Yen TJ, Hamilton AD, Sebti SM (2001) J Biol Chem 276:16161 CrossRefGoogle Scholar
  81. 81.
    Ashar HR, James L, Gray D, Carr D, Black S, Armstrong L, Bishop WR, Kirschmeier P (2000) J Biol Chem 275:30451 CrossRefGoogle Scholar
  82. 82.
    Li Q, Ke Y, Kapp JA, Fertig N, Medsger TA, Joshi HC (1995) Biochem Biophys Res Commun 212:220 CrossRefGoogle Scholar
  83. 83.
    Liao H, Winkfein RJ, Mack G, Rattner JB, Yen TJ (1995) J Cell Biol 130:507 CrossRefGoogle Scholar
  84. 84.
    Schaar BT, Chan GKT, Maddox P, Salmon ED, Yen TJ (1997) J Cell Biol 139:1373 CrossRefGoogle Scholar
  85. 85.
    Chan GK, Schaar BT, Yen TJ (1998) J Cell Biol 143:49 CrossRefGoogle Scholar
  86. 86.
    Moasser MM, Sepp-Lorenzino L, Kohl NE, Oliff A, Balog A, Su DS, Danishefsky SJ, Rosen N (1998) Proc Natl Acad Sci USA 95:1369 CrossRefGoogle Scholar
  87. 87.
    Shi B, Yaremko B, Hajian G, Terracina G, Bishop WR, Liu M, Nielsen LL (2000) Cancer Chemother Pharmacol 46:387 CrossRefGoogle Scholar
  88. 88.
    de Caestecker MP, Piek E, Roberts AB (2000) J Natl Cancer Inst 92:1388 CrossRefGoogle Scholar
  89. 89.
    Venkatasubbarao K, Ahmed MM, Mohiuddin M, Swiderski C, Lee E, Gower WR, Salhab KF, McGrath P, Strodel W, Freeman JW (2000) Anticancer Res 20:43 Google Scholar
  90. 90.
    Muro-Cacho CA, Rosario-Ortiz K, Livingston S, Munoz-Antonia T (2001) Clin Cancer Res 7:1618 Google Scholar
  91. 91.
    Matsushita M, Matsuzaki K, Date M, Watanabe T, Shibano K, Nakagawa T, Yanagitani S, Amoh Y, Takemoto H, Ogata N, Yamamoto C, Kubota Y, Seki T, Inokuchi H, Nishizawa M, Takada H, Sawamura T, Okamura A, Inoue K (1999) Br J Cancer 80:194 CrossRefGoogle Scholar
  92. 92.
    Brattain MG, Ko Y, Banerji SS, Wu G, Willson JK (1996) J Mammary Gland Biol Neoplasia 4:365 CrossRefGoogle Scholar
  93. 93.
    Hejlik DP, Kottickal LV, Liang H, Fairman J, Davis T, Janecki T, Sexton D, Peery W, Tavtigian SV, Teng DH, Nagarajan L (1997) Cancer Res 57:3779 Google Scholar
  94. 94.
    Adnane J, Bizouarn FA, Chen Z, Ohkanda J, Hamilton AD, Munoz-Antonia T, Sebti SM (2000) Oncogene 19:5525 CrossRefGoogle Scholar
  95. 95.
    Fralix KD, Jeske N, Freeman JW (2000) Proc Am Assoc Cancer Res 41:440 Google Scholar
  96. 96.
    Alcock RA, Dey S, Mohiuddin M, Gallicchio VS, Chatfield LK, Freeman JW (2001) Proc Am Assoc Cancer Res 42:489 Google Scholar
  97. 97.
    Basso AD, Mirza A, Liu G, Long BJ, Bishop WR, Kirshmeier P (2005) J Biol Chem 280:31101 CrossRefGoogle Scholar
  98. 98.
    Lebowitz PF, Sakamuro D, Prendergast GC (1997) Cancer Res 57:708 Google Scholar
  99. 99.
    Kohl NE, Omer CA, Conner MW, Anthony NJ, Davide JP, deSolms SJ, Giuliani EA, Gomez RP, Graham SL, Hamilton K, Handt LK, Hartman GD, Kobaln KS, Kral AM, Miller PJ, Mosser SD, O'Neill TJ, Rands E, Schaber MD, Gibbs JB, Oliff A (1995) Nat Med 1:792 CrossRefGoogle Scholar
  100. 100.
    Liu M, Bryant MS, Chen J, Lee S, Yaremko B, Lipari P, Malkowski M, Ferrari E, Nielsen L, Prioli N, Dell J, Sinha J, Syed J, Korfmacher WA, Nomeir AA, Lin CC, Wang L, Taveras AG, Doll RJ, Njoroge FG, Mallams AK, Remiszewski S, Catino JJ, Girijavallabahan VM, Kirschmeier P, Bishop WR (1998) Cancer Res 58:4947 Google Scholar
  101. 101.
    Jiang K, Coppola D, Crespo NC, Nicosia SV, Hamilton AD, Sebti SM, Cheng JQ (2000) Mol Cell Biol 20:139 CrossRefGoogle Scholar
  102. 102.
    Du W, Liu A, Prendergast GC (1999) Cancer Res 59:4208 Google Scholar
  103. 103.
    McFall A, Ulku A, Lambert QT, Kusa A, Rogers-Graham K, Der CJ (2001) Mol Cell Biol 21:5488 CrossRefGoogle Scholar
  104. 104.
    Ochiai N, Uchida R, Fuchida S, Okano A, Okamoto M, Ashihara E, Inaba T, Fujita N, Matsubara H, Shimazaki C (2003) Blood 102:3349 CrossRefGoogle Scholar
  105. 105.
    Birkencamp KU, Geugien M, Schepers H, Westra J, Lemmink HH, Vellenga E (2004) Leukemia 18:103 CrossRefGoogle Scholar
  106. 106.
    Takada Y, Khuri FR, Aggarawal BB (2004) J Biol Chem 279:26287 CrossRefGoogle Scholar
  107. 107.
    Mijimolle N, Velasco J, Dubus P, Guerra C, Weinbaum CA, Casey PJ, Campuzano V, Barbacid M (2005) Cancer Cell 7:313 CrossRefGoogle Scholar
  108. 108.
    Karp JE, Lancet JE, Kaufman SH, End DW, Wright JJ, Bol K, Horak I, Tidwell ML, Liesveld J, Kottke TJ, Ange DA, Buddharaju L, Gojo I, Highsmith E, Belly RT, Hohl RJ, Rybak ME, Thibault A, Rosenblatt J (2001) Blood 97:3361 CrossRefGoogle Scholar
  109. 109.
    Adjei AA, Erlichman C, David JN, Cutler DL, Sloan JA, Marks RS, Hanson LJ, Svinegn PA, Atherton P, Bishop WR, Kirschmeier P, Kaufman SH (2000) Cancer Res 60:1871 Google Scholar
  110. 110.
    Raponi M, Lowenberg B, Lancet JE, Harousseau JL, Stone R, Rackoff W, Thibault A, Zhang Y, Atkins D, Wang Y (2004) Blood 104:246A Google Scholar
  111. 111.
    Garcia AM, Rowell C, Ackermann K, Kowalczyk JJ, Lewis MD (1993) J Biol Chem 268:18415 Google Scholar
  112. 112.
    Kohl NE, Wilson FR, Mosser SD, Giuliani E, deSolms 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 USA 91:9141 CrossRefGoogle Scholar
  113. 113.
    Sun J, Qian Y, Hamilton AD, Sebti SM (1995) Cancer Res 55:4243 Google Scholar
  114. 114.
    Nagasu T, Yoshimatsu K, Rowell C, Lewis MD, Garcia AM (1995) Cancer Res 55:5310 Google Scholar
  115. 115.
    Vrignaud P, Bissery MC, Lavelle F (1999) Ann NY Acad Sci 886:249 CrossRefGoogle Scholar
  116. 116.
    Liu A, Prendergast GC (2000) FEBS Lett 481:205 CrossRefGoogle Scholar
  117. 117.
    Mazet JL, Padieu M, Osman H, Maume G, Mailliet P, Dereu N, Hamilton AD, Lavelle F, Sebti SM, Maume BF (1999) FEBS Lett 460:235 CrossRefGoogle Scholar
  118. 118.
    Yonemoto M, Satoh T, Arakawa H, Suzuki-Takahashi I, Monden Y, Kodera T, Tanaka K, Aoyama T, Iwasawa Y, Kamei T, Nishimura S, Tomimoto K (1998) Mol Pharmacol 54:1 Google Scholar
  119. 119.
    Aoyama T, Satoh T, Yonemoto M, Shibata J, Nonoshtia K, Arai S, Kawakami K, Iwasawa Y, Sano H, Tanaka K, Monden Y, Kodera T, Arakawa H, Suzuki-Takahashi I, Kamei T, Tomimoto K (1998) J Med Chem 41:143 CrossRefGoogle Scholar
  120. 120.
    Tahir SK, Gu WZ, Zang HC, Leal J, Lee JY, Kovar P, Saeed B, Cherian SP, Devine E, Cohen J, Warner R, Wang YC, Stout D, Arendsen DL, Rosenberg S, Ng SC (2000) Eur J Cancer 36:1161 CrossRefGoogle Scholar
  121. 121.
    Bottex-Gauthier C, Vidal D, Picot F, Potier P, Menichini F, Appendino G (1993) Biotechnol Ther 4:77 Google Scholar
  122. 122.
    Shaikenov TE, Adekenov SM, Williams RM, Prashad N, Baker FL, Madden TL, Newman R (2001) Oncol Rep 8:173 Google Scholar
  123. 123.
    Zujewski J, Horak ID, Bol CJ, Woestenborghs R, Bowden C, End DW, Piotrovsky VK, Chiao J, Belly RT, Todd A, Kopp WC, Kohler DR, Chow C, Noone M, Hakim FT, Larkin G, Gress RE, Nussenblatt RB, Kremer AB, Cowan KH (2000) J Clin Oncol 18:927 Google Scholar
  124. 124.
    Mallams AK, Rossman RR, Doll RJ, Girijavallabhan VM, Ganguly AK, Petrin J, Wang L, Patton R, Bishop WR, Carr DM, Kirschmeier P, Catino JJ, Bryant MS, Chen KJ, Korfmacher WA, Nardo C, Wang S, Nomeir AA, Lin CC, Li Z, Chen J, Lee S, Dell J, Lipari P, Malkowski M, Yaremko B, King I, Liu M (1998) J Med Chem 41:877 CrossRefGoogle Scholar
  125. 125.
    Strickland CL, Weber PC, Windsor WT, Wu Z, Le HV, Albanese MM, Alvarez CS, Cesarz D, del Rosario J, Deskus J, Mallams AK, Njoroge FG, Piwinski JJ, Remiszewski S, Rossman R, Taveras AG, Vibulbhan B, Doll RJ, Girijavallabhan VM, Ganguly AK (1999) J Med Chem 42:2125 CrossRefGoogle Scholar
  126. 126.
    Mallams AK, Njoroge FG, Doll RJ, Snow ME, Kaminski JJ, Rossman RR, Vibulbhan B, Bishop WR, Kirschmeier P, Liu M, Bryant MS, Alvarez C, Carr D, James L, King I, Li Z, Lin CC, Nardo C, Petrin J, Remiszewski SW, Taveras AG, Wang S, Wong J, Catino J, Girijavallabhan V, Ganguly AK (1997) Bioorg Med Chem 5:93 CrossRefGoogle Scholar
  127. 127.
    Njoroge FG, Taveras AG, Kelly J, Remiszewski S, Mallams AK, Wolin R, Afonso A, Cooper AB, Rane DF, Liu YT, Wong J, Vibulbhan B, Pinto P, Deskus J, Alvarez CS, Del Rosario J, Connolly M, Wang J, Desai J, Rossman RR, Bishop WR, Patton R, Wang L, Kirschmeier P, Bryant MS, Nomeir AA, Lin CC, Liu M, McPhail AT, Doll RJ, Girijavallabhan VM, Ganguly AK (1998) J Med Chem 41:4890 CrossRefGoogle Scholar
  128. 128.
    Njoroge FG, Vibulbhan B, Rane DF, Bishop WR, Petrin J, Patton R, Bryant MS, Chen KJ, Nomeir AA, Lin CC, Liu M, King I, Chen J, Lee S, Yaremko B, Dell J, Lipari P, Malkowski M, Li Z, Catino J, Doll RJ, Girijavallabhan V, Ganguly AK (1997) J Med Chem 40:4290 CrossRefGoogle Scholar
  129. 129.
    Kuo SC, Chen F, Hou D, Kim-Meade A, Bernard C, Liu J, Levy S, Wu GG (2003) J Org Chem 68:4984 CrossRefGoogle Scholar
  130. 130.
    Rokosz LL, Huang CY, Reader JC, Stauffer TM, Chelsky D, Sigal NH, Ganguly AK, Baldwin JJ (2005) Bioorg Med Chem Lett 15:5537 CrossRefGoogle Scholar
  131. 131.
    Huang CY, Stauffer TM, Strickland CL, Reader JC, Huang H, Li G, Cooper AB, Doll RJ, Ganguly AK, Baldwin JJ, Rokosz LL (2006) Bioorg Med Chem Lett 16:507 CrossRefGoogle Scholar
  132. 132.
    Njoroge FG, Vibulbhan B, Pinto P, Strickland CL, Bishop WR, Kirschmeier P, Girijavallabhan V, Ganguly AK (2003) Bioorg Med Chem 11:139 CrossRefGoogle Scholar
  133. 133.
    Njoroge FG, Vibulbhan B, Shi X, Strickland C, Kirschmeier P, Bishop WR, Nomeir A, Girijavallabhan V (2004) Bioorg Med Chem Lett 14:5899 CrossRefGoogle Scholar
  134. 134.
    Taveras AG, Aki C, Chao J, Doll RJ, Lalwani T, Girijavallabhan V, Strickland CL, Windsor WT, Weber P, Hollinger F, Snow M, Patton R, Kirschmeier P, James L, Liu M, Nomeir A (2002) J Med Chem 45:3854 CrossRefGoogle Scholar
  135. 135.
    Njoroge FG, Vibulbhan B, Pinto P, Strickland CL, Kirschmeier P, Bishop WR, Girijavallabhan V (2004) Bioorg Med Chem 14:5877 CrossRefGoogle Scholar
  136. 136.
    Njoroge FG, Vibulbhan B, Pinto P, Strickland C, Bishop WR, Nomeir A, Girijavallabhan V (2006) Bioorg Med Chem Lett 16:984 CrossRefGoogle Scholar
  137. 137.
    Venet M, End D, Angibaud P (2003) Curr Top Med Chem 3:1095 CrossRefGoogle Scholar
  138. 138.
    Reid TS, Beese LS (2004) Biochemistry 43:6877 CrossRefGoogle Scholar
  139. 139.
    Angibaud P, Bourdrez X, End DW, Freyne E, Janicot M, Lezouret P, Ligny Y, Mannens G, Damsch S, Mevellec L, Meyer C, Muller P, Pilatte I, Poncelet V, Roux B, Smets G, Van Dun J, Van Remoortere P, Venet M, Wouters W (2003) Bioorg Med Chem Lett 13:4365 CrossRefGoogle Scholar
  140. 140.
    Angibaud P, Bourdrez X, Devine A, End DW, Freyne E, Ligny Y, Muller P, Mannens G, Pilatte I, Poncelet V, Skrzat S, Smets G, Van Dun J, Van Remoortere P, Venet M, Wouters W (2003) Bioorg Med Chem Lett 13:1543 CrossRefGoogle Scholar
  141. 141.
    Skotnicki JS, Zask A, Nelson FC, Albright JD, Levin JI (1999) Ann NY Acad Sci 878:61 CrossRefGoogle Scholar
  142. 142.
    Hunt JT, Ding CZ, Batorsky R, Bednarz M, Bhide R, Cho Y, Chong S, Chao S, Gullo-Brown J, Guo P, Kim SH, Lee FY, Leftheris K, Miller A, Mitt T, Patel M, Penhallow BA, Ricca C, Rose WC, Schmidt R, Slusarchyk WA, Vite G, Manne W (2000) J Med Chem 43:3587 CrossRefGoogle Scholar
  143. 143.
    Johnston SRD (2003) IDrugs 6:72 Google Scholar
  144. 144.
    Lackner MR, Kindt RM, Carroll PM, Brown K, Cancilla MR, Chen C, de Silva H, Franke Y, Guan B, Heuer T, Hung T, Keegan K, Lee JM, Manne V, O'Brien C, Parry D, Perez-Villar JJ, Reddy RK, Xiao H, Zhan H, Cockett M, Plowman G, Fitzgerald K, Costa M, Ross-Macdonald P (2005) Cancer Cell 7:325 CrossRefGoogle Scholar
  145. 145.
    Camacho LH, Soignet SL, Pezzulli S, Canales C, Aghajanian C, Spriggs DS, Damle B, Sonnichsen D (2001) Proc Am Soc Clin Oncol 20:Abstract 311 Google Scholar
  146. 146.
    Lombardo LJ, Camuso A, Clark J, Fager K, Gullo-Brown J, Hunt JT, Inigo I, Kan D, Koplowitz B, Lee F, McGlinchey K, Qian L, Ricca C, Rovnyak G, Traeger S, Tokarski J, Williams DK, Wu LI, Zhao Y, Manne V, Bhide RS (2005) Bioorg Med Chem Lett 15:1895 CrossRefGoogle Scholar
  147. 147.
    Anthony NJ, Gomez RP, Schaber MD, Mosser SD, Hamilton KA, O'Neil TJ, Koblan KS, Graham SL, Hartman GD, Shah D, Rands E, Kohl NE, Gibbs JB, Oliff A (1999) J Med Chem 42:3356 CrossRefGoogle Scholar
  148. 148.
    Williams TM, Bergman JM, Brashear K, Breslin MJ, Dinsmore CJ, Hutchinson JH, MacTough SC, Stump CA, Wei DD, Zartman CB, Bogusky MJ, Culberson JC, Buser-Doepner C, Davide J, Greenberg IB, Hamilton KA, Koblan KS, Kohl NE, Liu D, Lobell RB, Mosser SD, O'Neill TJ, Rands E, Schaber MD, Wilson F, Senderak E, Motzel SL, Gibbs JB, Graham SL, Heimbrook DC, Hartman GD, Oliff AL, Huff JR (1999) J Med Chem 42:3779 CrossRefGoogle Scholar
  149. 149.
    Breslin MJ, deSolms SJ, Giuliani EA, Stokker GE, Graham SL, Pompliano DL, Mosser SD, Hamilton KA, Hutchinson JH (1998) Bioorg Med Chem 8:3311 CrossRefGoogle Scholar
  150. 150.
    Bell IM, Gallichio SN, Abrams M, Beshore DC, Buser CA, Culberson JC, Davide J, Ellis-Hutchings M, Fernandes C, Gibbs JB, Graham SL, Hartman GD, Heimbrook DC, Homnick CF, Huff JR, Kassahun K, Koblan KS, Kohl NE, Lobell RB, Lynch JJ, Miller PA, Omer CA, Rodrigues AD, Walsh ES, Williams TM (2001) J Med Chem 44:2933 CrossRefGoogle Scholar
  151. 151.
    Soignet S, Yao SL, Britten C, Spriggs D, Pezzulli S, McCreery H, Mazina K, Deutsch P, Lee Y, Lobell R, Rosen N, Rowinsky E (1998) Proc Am Assoc Cancer Res 40:517 Google Scholar
  152. 152.
    Britten CD, Rowinsky E, Yao SL, Soignet S, Rosen N, Eckhardt SG, Drengler R, Hammond L, Siu LL, Smith L, McCreery H, Pezzulli S, Lee Y, Lobell R, Deutsch P, Von Hoff D, Spriggs D (1999) Proc Am Soc Clin Oncol 18:597 Google Scholar
  153. 153.
    Reid TS, Long SB, Beese LS (2004) Biochemistry 43:9000 CrossRefGoogle Scholar
  154. 154.
    Lackner MR, Kindt RM, Carroll PM, Brown K, Cancilla MR, Chen C, de Silva H, Franke Y, Guan B, Heuer T, Hung T, Keegan K, Lee JM, Manne V, O'Brien C, Parry D, Perez-Villar JJ, Reddy RK, Xiao H, Zhan H, Cockett M, Plowman G, Fitzgerald K, Costa M, Ross-MacDonald P (2005) Cancer Cell 7:325 CrossRefGoogle Scholar
  155. 155.
    Bell IM, Gallicchio SN, Abrams M, Beese LS, Beshore DC, Bhimnathwala H, Bogusky MJ, Buser CA, Culberson JC, Davide J, Ellis-Hutchings M, Fernandes C, Gibbs JB, Graham SL, Hamilon KA, Hartman GD, Heimbrook DC, Homnick CF, Huber HE, Huff JR, Kassahun K, Koblan KS, Kohl NE, Lobell RB, Lynch JJ, Robinson R, Rodrigues AD, Taylor JS, Walsh ES, Williams TM, Zartman CB (2002) J Med Chem 45:2388 CrossRefGoogle Scholar
  156. 156.
    Dinsmore CJ, Zartman CB, Bergman JM, Abrams MT, Buser CA, Culberson JC, Davide JP, Ellis-Hutchings M, Fernandes C, Graham SL, Hartman GD, Huber HE, Lobell RB, Mosser SD, Robinson RG, Williams TM (2004) Bioorg Med Chem Lett 14:639 CrossRefGoogle Scholar
  157. 157.
    deSolms SJ, Ciccarone TM, MacTough SC, Shaw AW, Buser CA, Ellis-Hutchings M, Fernandes C, Hamilton KA, Huber HE, Kohl NE, Lobell RB, Robinson RG, Tsou NN, Walsh ES, Graham SL, Beese LS, Taylor JS (2003) J Med Chem 46:2973 CrossRefGoogle Scholar
  158. 158.
    Bergman JM, Abrams MT, Davide JP, Greenberg IB, Robinson RG, Buser CA, Huber HE, Koblan KS, Kohl NE, Lobell RB, Graham SL, Hartman GD, Williams TM, Dinsmore CJ (2001) Bioorg Med Chem Lett 11:1411 CrossRefGoogle Scholar
  159. 159.
    Henry KJ, Wasicak J, Tasker AS, Cohen J, Ewing P, Mitten M, Larsen JJ, Kalvin DM, Swenson R, Ng SC, Saeed B, Cherian S, Sham H, Rosenberg SH (1999) J Med Chem 42:4844 CrossRefGoogle Scholar
  160. 160.
    Curtin ML, Florjancic AS, Cohen J, Gu WZ, Frost DJ, Muchmore SW, Sham HL (2003) Bioorg Med Chem Lett 13:1367 CrossRefGoogle Scholar
  161. 161.
    Lin NH, Wang L, Cohen J, Gu WZ, Frost D, Zhang H, Rosenberg S, Sham H (2003) Bioorg Med Chem Lett 13:1293 CrossRefGoogle Scholar
  162. 162.
    Gwaltney SL, O'Connor SJ, Nelson LTJ, Sullivan GM, Imade H, Wang W, Hasvold L, Li Q, Cohen J, Gu WZ, Tahir SK, Bauch J, Marsh K, Ng SC, Frost DJ, Zhang H, Muchmore S, Jakob CG, Stoll V, Hutchins C, Rosenberg SH, Sham HL (2003) Bioorg Med Chem Lett 13:1363,1363 CrossRefGoogle Scholar
  163. 163.
    Tong Y, Lin NH, Wang L, Hasvold L, Wang W, Leonard N, Li T, Li Q, Cohen J, Gu WZ, Zhang H, Stoll V, Bauch J, Marsh K, Rosenberg SH, Sham HL (2003) Bioorg Med Chem Lett 13:1571 CrossRefGoogle Scholar
  164. 164.
    Hasvold LA, Wang W, Gwaltney SL, Rockway TW, Nelson LTJ, Mantei RA, Fakhoury SA, Sullivan GM, Li Q, Lin NH, Wang L, Zhang H, Cohen J, Gu WZ, Marsh K, Bauch J, Rosenberg SH, Sham HL (2003) Bioorg Med Chem Lett 13:4001 CrossRefGoogle Scholar
  165. 165.
    Wang L, Wang GT, Wang X, Tong Y, Sullivan G, Park D, Leonard NM, Li Q, Cohen J, Gu WZ, Zhang H, Bauch JL, Jakob CG, Hutchins CW, Stoll VS, Marsh K, Rosenberg SH, Sham HL, Lin NH (2004) J Med Chem 47:612 CrossRefGoogle Scholar
  166. 166.
    Wang L, Lin NH, Li Q, Henry RF, Zhang H, Cohen J, Gu WZ, Marsh KC, Bauch JL, Rosenberg SH, Sham HL (2004) Bioorg Med Chem Lett 14:4603 CrossRefGoogle Scholar
  167. 167.
    Li Q, Claiborne A, Li T, Hasvold L, Stoll VS, Muchmore S, Jakob CG, Gu W, Cohen J, Hutchins C, Frost D, Rosenberg SH, Sham HL (2004) Bioorg Med Chem Lett 14:5367 CrossRefGoogle Scholar
  168. 168.
    Li Q, Wang GT, Li T, Gwaltney SL, Woods KW, Claiborne A, Wang X, Gu W, Cohen J, Stoll VS, Hutchins C, Frost D, Rosenberg SH, Sham HL (2004) Bioorg Med Chem Lett 14:5371 CrossRefGoogle Scholar
  169. 169.
    Wang GT, Wang X, Wang W, Hasvold LA, Sullivan G, Hutchins CW, O'Conner S, Gentiles R, Sowin T, Cohen J, Gu WZ, Zhang H, Rosenberg SH, Sham HL (2005) Bioorg Med Chem Lett 15:153 CrossRefGoogle Scholar
  170. 170.
    Li Q, Woods KW, Wang W, Lin NH, Claiborne A, Gu WZ, Cohen J, Stoll VS, Hutchin C, Frost D, Rosenberg SH, Sham HL (2005) Bioorg Med Chem Lett 15:2033 CrossRefGoogle Scholar
  171. 171.
    Gu WZ, Joseph I, Wang YC, Frost D, Sullivan GM, Wang L, Lin NH, Cohen J, Stoll VS, Jakob CG, Muchmore SW, Harlan JE, Holzman T, Walten KA, Ladror US, Anderson MG, Kroeger P, Rodriguez LE, Jarvis KP, Ferguson D, Marsh K, Ng S, Rosenberg SH, Sham HL, Zhang H (2005) Anticancer Drugs 16:1069 Google Scholar
  172. 172.
    Rozema MJ, Kruger AW, Rohde BD, Shelat B, Bhagavatula L, Tien JJ, Zhang W, Henry RF (2005) Tetrahedron 61:4419 CrossRefGoogle Scholar
  173. 173.
    Ferguson D, Rodriguez LE, Palma JP, Refici M, Jarvis K, O'Connor J, Sullivan GM, Frost D, Marsh K, Bauch J, Zhang H, Lin NH, Rosenberg S, Sham HL, Joseph IBJK (2005) Clin Cancer Res 11:3045 CrossRefGoogle Scholar
  174. 174.
    Angibaud P, Saha AK, Bourdrez X, End DW, Freyne E, Lezouret P, Mannens G, Mevellec L, Meyer C, Pilatte I, Poncelet V, Roux B, Smet G, Van Dun J, Venet M, Wouters W (2003) Bioorg Med Chem Lett 13:4361 CrossRefGoogle Scholar
  175. 175.
    Prevost GP, Pradines A, Brezak MC, Lonchampt MO, Viossat I, Ader I, Toulas C, Kasprzyk P, Gordon T, Favre G, Morgan B (2001) Int J Cancer 91:718 CrossRefGoogle Scholar
  176. 176.
    Perez M, Maraval C, Dumont S, Lamothe M, Schambel P, Etievant C, Hill B (2003) Bioorg Med Chem Lett 13:1455 CrossRefGoogle Scholar
  177. 177.
    Le Diguarher T, Ortuno JC, Dorey G, Shanks D, Guilbaud N, Pierre A, Fauchere JL, Hickman JA, Tucker GC, Casara PJ (2003) Bioorg Med Chem 11:3193 CrossRefGoogle Scholar
  178. 178.
    Le Diguarher T, Ortuno JC, Shanks D, Guilbaud N, Pierre A, Raimbaud E, Fauchere JL, Hickman JA, Tucker GC, Casara PJ (2004) Bioorg Med Chem Lett 14:767 CrossRefGoogle Scholar
  179. 179.
    Smith AC, Tosca PJ, Prezioso J, Grossi I, Ryan M, Zutshi A, Lee S, Son WC, Juhn SH, Tomaszewski JE, Turner N (2001) Proc Am Assoc Cancer Res 42:489 Google Scholar
  180. 180.
    Sorbera LA, Fernandez R, Castaner JR (2001) Drugs Future 26:453 CrossRefGoogle Scholar
  181. 181.
    McCormack P, Macpherson M, Wilson D, Lindsay A, Parry T, Holt A, Hughes AJ (2004) Clin Oncol 22:3172 CrossRefGoogle Scholar
  182. 182.
    Press release from Ninth Annual JP Morgan H&Q Investing in Biotechnology Conference, July 2001, London Google Scholar
  183. 183.
    Lyssikatos JP, La Greca SD, Yang BV (2000) Quinolin-2-one derivitives useful as anticancer agents. WO 00/12498 Google Scholar
  184. 184.
    Patnaik A, Rowinsky EK (2001) Early clinical experience with farnesyl protein transferase inhibitors. In: Sebti SM, Hamilton AD (eds) Farnesyltransferase inhibitors in cancer therapy. Humana, Totowa, NJ, pp 233–249 Google Scholar
  185. 185.
    Hahn SM, Bernhard E, McKenna WG (2001) Semin Oncol 28:86 CrossRefGoogle Scholar
  186. 186.
    Schellens JHM, de Klerk G, Swart M, Palmer PA, Bol CJ, van't Veer LJ, Tan S, de Gast GC, Beijnen JH, ten Bokkel Huinink W (2000) Proc Am Soc Clin Oncol 19:715 Google Scholar
  187. 187.
    Johnson SR, Hickish T, Houston S, Ellis PA, Howes A, Thibualt A (2002) Proc Am Soc Clin Oncol 21:138 Google Scholar
  188. 188.
    Cloughesy TF, Kuhn J, Wen P, Chang SM, Schiff D, Greenberg H, Junck L, Robins I, DeAngelis LM, Yung A, Groves M, Fink K, Abrey LE, Lieberman F, Mehta MP, Raizer JJ, Hess K, Prados M (2002) Proc Am Soc Clin Oncol 21:317 Google Scholar
  189. 189.
    Kurzrock R, Albitar M, Cortes JE, Estey EH, Faderl SH, Garcia-Manero G, Thomas DA, Giles FJ, Ryback ME, Thibault A, De Porre P, Kantarjian HM (2004) J Clin Oncol 22:1287 CrossRefGoogle Scholar
  190. 190.
    Lancet JE, Karp JE (2003) Blood 102:3880 CrossRefGoogle Scholar
  191. 191.
    Karp JE, Lancet JE (2005) Curr Mol Med 5:643 CrossRefGoogle Scholar
  192. 192.
    Caponigro F, Casale M, Bryce J (2003) Expert Opin Investig Drugs 12:943 CrossRefGoogle Scholar
  193. 193.
    Jabbour E, Kantarjian H, Cortes J (2004) Leuk Lymphoma 45:2187 CrossRefGoogle Scholar
  194. 194.
    Appels NMGM, Beijnen JH, Schellens JHM (2005) Oncologist 10:565 CrossRefGoogle Scholar
  195. 195.
    Yokoyama K, Lin Y, Stuart KD, Gelb MH (1997) Mol Biochem Parasitol 87:61 CrossRefGoogle Scholar
  196. 196.
    Field H, Blench I, Croft S, Field MC (1996) Mol Biochem Parasitol 82:67 CrossRefGoogle Scholar
  197. 197.
    Yokoyama K, Trobridge P, Buckner FS, Scholten J, Stuart KD, Van Voorhis WC, Gelb MH (1998) Mol Biochem Parasitol 94:87 CrossRefGoogle Scholar
  198. 198.
    Chakrabarti D, Azam T, DelVecchio C, Qiu L, Park Y, Allen CM (1998) Mol Biochem Parasitol 94:175 CrossRefGoogle Scholar
  199. 199.
    Yokoyama K, Trobridge P, Buckner FS, Van Voorhis WC, Stuart KD, Gelb MH (1998) J Biol Chem 273:26497 CrossRefGoogle Scholar
  200. 200.
    Chakrabarti D, Da Silva T, Barger J, Paquette S, Patel H, Patterson S, Allen CM (2002) J Biol Chem 277:42066 CrossRefGoogle Scholar
  201. 201.
    Gelb MH, Van Voorhis WC, Buckner FS, Yokoyama K, Eastman R, Carpenter EP, Panethymitaki C, Brown KA, Smith DF (2003) Mol Biochem Parasitol 126:155 CrossRefGoogle Scholar
  202. 202.
    Nallan L, Bauer KD, Bendale P, Rivas K, Yokoyama K, Horney CP, Pendyala PR, Floyd D, Lombardo LJ, Williams DK, Hamilton A, Sebti S, Windsor WT, Weber PC, Buckner FS, Chakrabarti D, Gelb MH, Van Voorhis WC (2005) J Med Chem 48:3704 CrossRefGoogle Scholar
  203. 203.
    Schlitzer M (2005) Curr Med Chem Anti-Infective Agents 4:277 CrossRefGoogle Scholar
  204. 204.
    Glenn MP, Chang SY, Hucke O, Verlinde CLMJ, Rivas K, Horney C, Yokoyama K, Buckner FS, Pendyala PR, Chakrabarti D, Gelb M, Van Voorhis WC, Sebti SM, Hamilton AD (2005) Angew Chem Int Ed Engl 44:4903 CrossRefGoogle Scholar
  205. 205.
    Kettler K, Sakowski J, Wiesner J, Ortmann R, Jomaa H, Schlitzer M (2005) Pharmazie 60:323 Google Scholar
  206. 206.
    Kettler K, Wiesner J, Fucik K, Sakowski J, Ortmann R, Dahse HM, Jomaa H, Schlitzer M (2005) Pharmazie 60:677 Google Scholar
  207. 207.
    Ryckebusch A, Gilleron P, Millet R, Houssin R, Lemoine A, Pommery N, Grellier P, Sergheraert C, Henichart JP (2005) Chem Pharm Bull 53:1324 CrossRefGoogle Scholar
  208. 208.
    Buckner FS, Yokoyama K, Nguyen L, Grewal A, Erdjument-Bromage H, Tempst P, Strickland CL, Xiao L, Van Voorhis WC, Gelb MH (2000) J Biol Chem 275:21870 CrossRefGoogle Scholar
  209. 209.
    Ohkanda J, Buckner FS, Lockman JW, Yokoyama K, Carrico D, Eastman R, De Lucas-Fradley K, Davies W, Croft SL, Van Voorhis WC, Gelb MH, Sebti SM, Hamilton AD (2004) J Med Chem 47:432 CrossRefGoogle Scholar
  210. 210.
    Esteva MI, Kettler K, Maidana C, Fichera L, Ruiz AM, Bontempi EJ, Andersson B, Dashe HM, Haebel P, Ortmann R, Klebe G, Schlitzer M (2005) J Med Chem 48:7186 CrossRefGoogle Scholar
  211. 211.
    Hucke O, Gelb MH, Verlinde CLMJ, Buckner FS (2005) J Med Chem 48:5415 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  1. 1.Early DevelopmentJohnson & Johnson Pharmaceutical Research & DevelopmentSpringhouseUSA
  2. 2.Department of Medicinal ChemistryJohnson & Johnson Pharmaceutical Research & DevelopmentVal de ReuilFrance

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