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Chemical Compound Review

Zarnestra     6-[(R)-amino-(4- chlorophenyl)-(3...

Synonyms: Tipifarneb, Tipifarnib, SureCN8097, PubChem22490, S1453_Selleck, ...
 Abrey,  Siegel-Lakhai,  Robins,  Gore,  Loonen, Shira Hoschander, Daphne A. Haas-Kogan,  Kaspers,  Clark,  Crul,  Chow,  Post,  Jayaprakash,  Fink, Said M. Sebti,  Cohen,  Karasek,  Goemans,  Pluim,  Perez Ruixo,  Bonanno,  Lebowitz,  Gibson,  Zhang,  Lamborn,  Szawlowski,  Signore,  Howes,  Widemann,  Slegers,  Lahorte, Christine Pellegrino, John J. Wright,  Dierckx,  Schellens,  Kuhn,  Chang,  Ma,  Belly,  Persky,  Schiff, J. Russell Geyer,  De Porre, Tina Young Poussaint,  Cloughesy,  O'bryant,  Mikule,  Sparidans, Maryam Fouladi,  Kersemans,  Khuri, Domenico Coppola,  Vervenne,  Pierson, Aslamuzzaman Kazi,  Zhang,  Hayes,  Piotrovsky, Michael D. Prados, Tracy McKnight,  Van Cutsem,  Zannikos,  Beijnen, David S. Hong, Said M. Sebti, Robert A. Newman, Michelle A. Blaskovich, Lei Ye, Robert F. Gagel, Stacy Moulder, Jennifer J. Wheler, Aung Naing, Nizar M. Tannir, Chaan S. Ng, Steven I. Sherman, Adel K. El Naggar, Rabia Khan, Jon Trent, John J. Wright, Razelle Kurzrock,  Palmer,  Morrow,  Piotrovskij,  DeAngelis,  Gustafson, Tianhong Li,  Harlow, Mokenge Malafa,  Franc, Abdissa Negassa,  Junck,  McLeod,  Atkins,  Lieberman,  Zwaan,  Ozdemir,  Verweij,  Zannikos, James M. Boyett,  Francke, Anuradha Banerjee,  Heinrich, Joseph A. Sparano, Stacy Moulder,  Mehta,  Solanki,  Zhang,  Creutzig,  Capriotti,  Oettle,  Karp,  Neumann,  Paquette, Sofia Merajver, David Lee,  Humblet, Pam Munster,  Wang,  Reinhardt, Susan M. Blaney,  Venzon,  Cornelissen,  Mathijssen,  Lancet,  Eckhardt,  Sparreboom,  Wen,  Hählen,  Groves, Una Hopkins,  Mesa, Larry E. Kun, Alberto Broniscer,  Wright,  Van de Wiele,  Eng-Wong,  Schoffski,  Raponi, Linda Vahdat,  Holden,  Gantz,  Von Hoff,  Prados,  Perez-Ruixo,  Marsh,  Balis,  Sebti,  Yung, Dawn Hershman, Mehmet Kocak, Celina Kleer, Susan Fineberg,  van de Velde,  Perez-Ruixo,  Zujewski,  Verslype,  Safran,  
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Disease relevance of Zarnestra


High impact information on Zarnestra


Chemical compound and disease context of Zarnestra


Biological context of Zarnestra


Anatomical context of Zarnestra

  • In the present study we report that tipifarnib used at pharmacologically achievable concentrations strongly inhibits the erythroid burst-forming unit (BFU-E) autonomous growth that characterizes patients with PV [3].
  • The farnesyl transferase inhibitor, tipifarnib, is a potent inhibitor of the MDR1 gene product, P-glycoprotein, and demonstrates significant cytotoxic synergism against human leukemia cell lines [12].
  • The STOP trial objectives are to evaluate the effect of gefitinib and tipifarnib on histologic and biologic parameters in patients with evidence of sputum atypia, to evaluate various parameters as potential predictors of the effectiveness of these agents, and to evaluate the tolerability of these agents over a 6-month course of treatment [14].

Associations of Zarnestra with other chemical compounds


Gene context of Zarnestra


Analytical, diagnostic and therapeutic context of Zarnestra


  1. In vitro profiling of the sensitivity of pediatric leukemia cells to tipifarnib: identification of T-cell ALL and FAB M5 AML as the most sensitive subsets. Goemans, B.F., Zwaan, C.M., Harlow, A., Loonen, A.H., Gibson, B.E., Hählen, K., Reinhardt, D., Creutzig, U., Heinrich, M.C., Kaspers, G.J. Blood (2005) [Pubmed]
  2. Farnesyltransferase inhibitor tipifarnib is well tolerated, induces stabilization of disease, and inhibits farnesylation and oncogenic/tumor survival pathways in patients with advanced multiple myeloma. Alsina, M., Fonseca, R., Wilson, E.F., Belle, A.N., Gerbino, E., Price-Troska, T., Overton, R.M., Ahmann, G., Bruzek, L.M., Adjei, A.A., Kaufmann, S.H., Wright, J.J., Sullivan, D., Djulbegovic, B., Cantor, A.B., Greipp, P.R., Dalton, W.S., Sebti, S.M. Blood (2004) [Pubmed]
  3. Farnesyltransferase inhibitor tipifarnib (R115777) preferentially inhibits in vitro autonomous erythropoiesis of polycythemia vera patient cells. Larghero, J., Gervais, N., Cassinat, B., Rain, J.D., Schlageter, M.H., Padua, R.A., Chomienne, C., Rousselot, P. Blood (2005) [Pubmed]
  4. Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. Van Cutsem, E., van de Velde, H., Karasek, P., Oettle, H., Vervenne, W.L., Szawlowski, A., Schoffski, P., Post, S., Verslype, C., Neumann, H., Safran, H., Humblet, Y., Perez Ruixo, J., Ma, Y., Von Hoff, D. J. Clin. Oncol. (2004) [Pubmed]
  5. Phase I trial of tipifarnib in patients with recurrent malignant glioma taking enzyme-inducing antiepileptic drugs: a North American Brain Tumor Consortium Study. Cloughesy, T.F., Kuhn, J., Robins, H.I., Abrey, L., Wen, P., Fink, K., Lieberman, F.S., Mehta, M., Chang, S., Yung, A., DeAngelis, L., Schiff, D., Junck, L., Groves, M., Paquette, S., Wright, J., Lamborn, K., Sebti, S.M., Prados, M. J. Clin. Oncol. (2005) [Pubmed]
  6. Phase I trial of tipifarnib in children with newly diagnosed intrinsic diffuse brainstem glioma. Haas-Kogan, D.A., Banerjee, A., Kocak, M., Prados, M.D., Geyer, J.R., Fouladi, M., McKnight, T., Poussaint, T.Y., Broniscer, A., Blaney, S.M., Boyett, J.M., Kun, L.E. Neuro-oncology (2008) [Pubmed]
  7. Phase II trial of tipifarnib plus neoadjuvant doxorubicin-cyclophosphamide in patients with clinical stage IIB-IIIC breast cancer. Sparano, J.A., Moulder, S., Kazi, A., Coppola, D., Negassa, A., Vahdat, L., Li, T., Pellegrino, C., Fineberg, S., Munster, P., Malafa, M., Lee, D., Hoschander, S., Hopkins, U., Hershman, D., Wright, J.J., Kleer, C., Merajver, S., Sebti, S.M. Clin. Cancer Res. (2009) [Pubmed]
  8. A phase I trial and pharmacokinetic study of tipifarnib, a farnesyltransferase inhibitor, and tamoxifen in metastatic breast cancer. Lebowitz, P.F., Eng-Wong, J., Widemann, B.C., Balis, F.M., Jayaprakash, N., Chow, C., Clark, G., Gantz, S.B., Venzon, D., Zujewski, J. Clin. Cancer Res. (2005) [Pubmed]
  9. Tipifarnib and bortezomib are synergistic and overcome cell adhesion-mediated drug resistance in multiple myeloma and acute myeloid leukemia. Yanamandra, N., Colaco, N.M., Parquet, N.A., Buzzeo, R.W., Boulware, D., Wright, G., Perez, L.E., Dalton, W.S., Beaupre, D.M. Clin. Cancer Res. (2006) [Pubmed]
  10. A phase I safety, pharmacological and biological study of the farnesyl protein transferase inhibitor, tipifarnib and capecitabine in advanced solid tumors. Gore, L., Holden, S., Cohen, R., Morrow, M., Pierson, A., O'bryant, C., Persky, M., Gustafson, D., Mikule, C., Zhang, S., Palmer, P., Eckhardt, S. Ann. Oncol. (2006) [Pubmed]
  11. The influence of farnesyl protein transferase inhibitor R115777 (Zarnestra) alone and in combination with purine nucleoside analogs on acute myeloid leukemia progenitors in vitro. Korycka, A., Smolewski, P., Robak, T. Eur. J. Haematol. (2004) [Pubmed]
  12. The farnesyl transferase inhibitor, tipifarnib, is a potent inhibitor of the MDR1 gene product, P-glycoprotein, and demonstrates significant cytotoxic synergism against human leukemia cell lines. Medeiros, B.C., Landau, H.J., Morrow, M., Lockerbie, R.O., Pitts, T., Eckhardt, S.G. Leukemia (2007) [Pubmed]
  13. Prevention of mouse lung tumors and modulation of DNA methylation by combined treatment with budesonide and R115777 (ZarnestraMT). Alyaqoub, F.S., Tao, L., Kramer, P.M., Steele, V.E., Lubet, R.A., Gunning, W.T., Pereira, M.A. Carcinogenesis (2007) [Pubmed]
  14. Primary and secondary prevention of non-small-cell lung cancer: the SPORE Trials of Lung Cancer Prevention. Khuri, F.R. Clinical lung cancer. (2003) [Pubmed]
  15. Establishment and characterization of acquired resistance to the farnesyl protein transferase inhibitor R115777 in a human colon cancer cell line. Smith, V., Rowlands, M.G., Barrie, E., Workman, P., Kelland, L.R. Clin. Cancer Res. (2002) [Pubmed]
  16. Phase I and pharmacological study of the farnesyltransferase inhibitor tipifarnib (Zarnestra, R115777) in combination with gemcitabine and cisplatin in patients with advanced solid tumours. Siegel-Lakhai, W.S., Crul, M., Zhang, S., Sparidans, R.W., Pluim, D., Howes, A., Solanki, B., Beijnen, J.H., Schellens, J.H. Br. J. Cancer (2005) [Pubmed]
  17. Phase I trial of a combination of the multikinase inhibitor sorafenib and the farnesyltransferase inhibitor tipifarnib in advanced malignancies. Hong, D.S., Sebti, S.M., Newman, R.A., Blaskovich, M.A., Ye, L., Gagel, R.F., Moulder, S., Wheler, J.J., Naing, A., Tannir, N.M., Ng, C.S., Sherman, S.I., El Naggar, A.K., Khan, R., Trent, J., Wright, J.J., Kurzrock, R. Clin. Cancer Res. (2009) [Pubmed]
  18. Anti-inflammatory activity in vitro and in vivo of the protein farnesyltransferase inhibitor tipifarnib. Xue, X., Lai, K.T., Huang, J.F., Gu, Y., Karlsson, L., Fourie, A. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  19. Pharmacogenetics of tipifarnib (R115777) transport and metabolism in cancer patients. Sparreboom, A., Marsh, S., Mathijssen, R.H., Verweij, J., McLeod, H.L. Investigational new drugs. (2004) [Pubmed]
  20. Effect of CYP2D6 genetic polymorphism on the population pharmacokinetics of tipifarnib. Perez-Ruixo, J.J., Zannikos, P., Ozdemir, V., Franc, M.A., Francke, S., Piotrovsky, V. Cancer Chemother. Pharmacol. (2006) [Pubmed]
  21. Pharmacokinetics of tipifarnib after oral and intravenous administration in subjects with advanced cancer. Zhang, S., Zannikos, P., Awada, A., Piccart-Gebhart, M., Dirix, L.Y., Fumoleau, P., Verhaeghe, T., Francois, M., De Porre, P. Journal of clinical pharmacology. (2006) [Pubmed]
  22. Population pharmacokinetics of tipifarnib in healthy subjects and adult cancer patients. Perez-Ruixo, J.J., Piotrovskij, V., Zhang, S., Hayes, S., De Porre, P., Zannikos, P. British journal of clinical pharmacology. (2006) [Pubmed]
  23. In vivo apoptosis detection with radioiodinated Annexin V in LoVo tumour-bearing mice following Tipifarnib (Zarnestra, R115777) farnesyltransferase inhibitor therapy. Cornelissen, B., Lahorte, C., Kersemans, V., Capriotti, G., Bonanno, E., Signore, A., Van de Wiele, C., Dierckx, R.A., Slegers, G. Nucl. Med. Biol. (2005) [Pubmed]
  24. Tipifarnib: farnesyl transferase inhibition at a crossroads. Mesa, R.A. Expert review of anticancer therapy. (2006) [Pubmed]
  25. Microarray analysis reveals genetic pathways modulated by tipifarnib in acute myeloid leukemia. Raponi, M., Belly, R.T., Karp, J.E., Lancet, J.E., Atkins, D., Wang, Y. BMC Cancer (2004) [Pubmed]
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