Azacyclic FTY720 Analogues That Limit Nutrient Transporter Expression but Lack S1P Receptor Activity and Negative Chronotropic Effects Offer a Novel and Effective Strategy to Kill Cancer Cells in Vivo

ACS Chemical Biology

Volumn 11, Issue 2, 2016, Pages 409-414

  Chen, Bin ^a   Roy, Saurabh G ^b   McMonigle, Ryan J ^b   Keebaugh, Andrew ^b   McCracken, Alison N ^b   Selwan, Elizabeth ^b   Fransson, Rebecca ^a   Fallegger, Daniel ^c   Huwiler, Andrea ^c   Kleinman, Michael T ^b   Edinger, Aimee L ^b   Hanessian, Stephen ^a  

^a UNIVERSITÉ DE MONTRÉAL   (Canada)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF BERN   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

FINGOLIMOD; SPHINGOSINE 1 PHOSPHATE RECEPTOR; ANTINEOPLASTIC AGENT; CARRIER PROTEIN; IMMUNOSUPPRESSIVE AGENT; PYRROLIDINE DERIVATIVE;

ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER CELL LINE; CANCER CELL; CANCER GROWTH; CELL PROLIFERATION; CELL VIABILITY; CHRONOTROPISM; COLON CANCER; CONTROLLED STUDY; DIASTEREOISOMER; DOWN REGULATION; ENANTIOMER; FLOW CYTOMETRY; HEART RATE; HUMAN; HUMAN CELL; IC50; IN VITRO STUDY; IN VIVO STUDY; LEUKEMIA CELL; LUNG CANCER CELL LINE; MALE; MOUSE; NONHUMAN; PANCREATIC CANCER CELL LINE; PRIORITY JOURNAL; PROSTATE CANCER CELL LINE; PROTEIN EXPRESSION; PROTEIN FUNCTION; STATIC ELECTRICITY; STEREOCHEMISTRY; TUMOR XENOGRAFT; ANALOGS AND DERIVATIVES; ANIMAL; CHEMISTRY; METABOLISM; NEOPLASMS; NUDE MOUSE; PATHOLOGY; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; CARRIER PROTEINS; CELL LINE, TUMOR; FINGOLIMOD HYDROCHLORIDE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; MICE, NUDE; NEOPLASMS; PYRROLIDINES; RECEPTORS, LYSOSPHINGOLIPID;

EID: 84959349238     PISSN: 15548929     EISSN: 15548937     Source Type: Journal    
DOI: 10.1021/acschembio.5b00761     Document Type: Article

References (23)

1. Brinkmann, V. (2009) FTY720 (fingolimod) in Multiple Sclerosis: Therapeutic effects in the immune and the central nervous system Br. J. Pharmacol. 158, 1173-1182 10.1111/j.1476-5381.2009.00451.x
2. Brinkmann, V., Billich, A., Baumruker, T., Heining, P., Schmouder, R., Francis, G., Aradhye, S., and Burtin, P. (2010) Fingolimod (FTY720): Discovery and development of an oral drug to treat multiple sclerosis Nat. Rev. Drug Discovery 9, 883-897 10.1038/nrd3248
3. Sanford, M. (2014) Fingolimod: A Review of Its Use in Relapsing-Remitting Multiple Sclerosis Drugs 74, 1411-1433 10.1007/s40265-014-0264-y
4. Mandala, S., Hajdu, R., Bergstrom, J., Quackenbush, E., Xie, J., Milligan, J., Thornton, R., Shei, G. J., Card, D., Keohane, C., Rosenbach, M., Hale, J., Lynch, C., Thornton, R., Shei, G. J., Card, D., Keohane, C., Rosenbach, M., Hale, J., Lynch, C. L., Rupprecht, K., Parsons, W., and Rosen, H. (2002) Alteration of Lymphocyte Trafficking by Sphingosine-1-Phosphate Receptor Agonists Science 296, 346-349
5. Brinkmann, V., Davis, M. D., Heise, C. E., Albert, R., Cottens, S., Hof, R., Bruns, C., Prieschl, E., Baumruker, T., Hiestand, P., Foster, C. A., Zollinger, M., and Lynch, K. R. (2002) The immune modulator FTY720 targets sphingosine 1-phosphate receptors J. Biol. Chem. 277, 21453-21457 10.1074/jbc.C200176200
6. Zemann, B., Kinzel, B., Müller, M., Reuschel, R., Mechtcheriakova, D., Urtz, N., Bornancin, F., Baumruker, T., and Billich, A. (2006) Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720 Blood 107, 1454 10.1182/blood-2005-07-2628
7. Lee, T. K., Man, K., Ho, J. W., Wang, X. H., Poon, R. T., Xu, Y., Ng, K. T., Chu, A. C., Sun, C. K., Ng, I. O., Sun, H. C., Tang, Z. Y., Xu, R., and Fan, S. T. (2005) FTY720: A Promising Agent for Treatment of Metastatic Hepatocellular Carcinoma Clin. Cancer Res. 11, 8458-8466 10.1158/1078-0432.CCR-05-0447
8. Azuma, H., Takahara, S., Ichimaru, N., Wang, J. D., Itoh, Y., Otsuki, Y., Morimoto, J., Fukui, R., Hoshiga, M., Ishihara, T., Nonomura, N., Suzuki, S., Okuyama, A., and Katsuoka, Y. (2002) Marked Prevention of Tumor Growth and Metastasis by a Novel Immunosuppressive Agent, FTY720, in Mouse Breast Cancer Models Cancer Res. 62, 1410-1419
9. Chua, C. W., Lee, D. T., Ling, M. T., Zhou, C., Man, K., Ho, J., Chan, F. L., Wang, X., and Wong, Y. C. (2005) FTY720, a fungus metabolite, inhibits in vivo growth of androgen-independent prostate cancer Int. J. Cancer 117, 1039-1048 10.1002/ijc.21243
10. Azuma, H., Takahara, S., Horie, S., Muto, S., Otsuki, Y., and Katsuoka, Y. (2003) Induction of Apoptosis in Human Bladder Cancer Cells In Vitro and In Vivo Caused by FTY720 Treatment J. Urol. 169, 2372-2377 10.1097/01.ju.0000064938.32318.91
11. Neviani, P., Santhanam, R., Oaks, J. J., Eiring, A. M., Notari, M., Blaser, B. W., Liu, S., Trotta, R., Muthusamy, N., Gambacorti-Passerini, C., Druker, B. J., Cortes, J., Marcucci, G., Chen, C. S., Verrills, N. M., Roy, D. C., Caligiuri, M. A., Bloomfield, C. D., Byrd, J. C., and Perrotti, D. (2007) FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemia J. Clin. Invest. 117, 2408-2421 10.1172/JCI31095
12. Camm, J., Hla, T., Bakshi, R., and Brinkmann, V. (2014) Cardiac and vascular effects of fingolimod: Mechanistic basis and clinical implications Am. Heart J. 168, 632-644 10.1016/j.ahj.2014.06.028
13. Cohen, J. A. And Chun, J. (2011) Mechanisms of fingolimod's efficacy and adverse effects in multiple sclerosis Ann. Neurol. 69, 759-777 10.1002/ana.22426
14. Sanna, M.G., Liao, J., Jo, E., Alfonso, C., Ahn, M. Y., Peterson, M. S., Webb, B., Lefebvre, S., Chun, J., Gray, N., and Rosen, H. (2004) Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate J. Biol. Chem. 279, 13839-13848 10.1074/jbc.M311743200
15. Forrest, M., Sun, S. Y., Hajdu, R., Bergstrom, J., Card, D., Doherty, G., Hale, J., Keohane, C., Meyers, C., Milligan, J., Mills, S., Nomura, N., Rosen, H., Rosenbach, M., Shei, G. J., Singer, I. I., Tian, M., West, S., White, V., Xie, J., Proia, R. L., and Mandala, S. (2004) Immune Cell Regulation and Cardiovascular Effects of Sphingosine 1-Phosphate Receptor Agonists in Rodents Are Mediated via Distinct Receptor Subtypes J. Pharmacol. Exp. Ther. 309, 758-768
16. Romero Rosales, K., Singh, G., Wu, K., Chen, J., Janes, M. R., Lilly, M. B., Peralta, E. R., Siskind, L. J., Bennett, M. J., Fruman, D. A., and Edinger, A. L. (2011) Sphingolipid-based drugs selectively kill cancer cells by down-regulating nutrient transporter proteins Biochem. J. 439, 299-311 10.1042/BJ20110853
17. Guenther, G. G., Peralta, E. R., Rosales, K. M., Wong, S. Y., Siskind, L. J., and Edinger, A. L. (2008) Proc. Natl. Acad. Sci. U. S. A. 105, 17402-17407 10.1073/pnas.0802781105
18. Welsch, C. A., Roth, L. W., Goetschy, J. F., and Movva, N. R. (2004) J. Biol. Chem. 279, 36720-36731 10.1074/jbc.M406179200
19. Hanessian, S., Charron, G., Billich, A., and Guerini, D. (2007) Constrained azacyclic analogues of the immunomodulatory agent FTY720 as molecular probes for sphingosine 1-phosphate receptors Bioorg. Med. Chem. Lett. 17, 491-494 10.1016/j.bmcl.2006.10.014
20. 1 receptor agonist Bioorg. Med. Chem. Lett. 15, 3568-3572 10.1016/j.bmcl.2005.05.097
21. Davis, M. D., Clemens, J. J., Macdonald, T. L., and Lynch, K. R. (2005) Sphingosine 1-Phosphate Analogs as Receptor Antagonists J. Biol. Chem. 280, 9833-9841 10.1074/jbc.M412356200
22. Zhu, R., Snyder, A. H., Kharel, Y., Schaffter, L., Sun, Q., Kennedy, P. C., Lynch, K. R., and Macdonald, T. L. (2007) Asymmetric Synthesis of Conformationally Constrained Fingolimod Analogues-Discovery of an Orally Active Sphingosine 1-Phosphate Receptor Type-1 Agonist and Receptor Type-3 Antagonist J. Med. Chem. 50, 6428-6435 10.1021/jm7010172
23. Fransson, R., McCracken, A. N., Chen, B., McMonigle, R. J., Edinger, A. L., and Hanessian, S. (2013) Design, Synthesis, and Anti-leukemic Activity of Stereochemically Defined Constrained Analogs of FTY720 (Gilenya) ACS Med. Chem. Lett. 4, 969-973 10.1021/ml4002425