The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Ozanimod (RPC1063) is a potent sphingosine‐1‐phosphate receptor‐1 (S1P 1 ) and receptor‐5 (S1P 5 ) agonist with autoimmune disease‐modifying activity
Open accessAbstract
Background and Purpose: Sphingosine1‐phosphate (S1P) receptors mediate multiple events including lymphocyte trafficking, cardiac function, and endothelial barrier integrity. Stimulation of S1P 1 receptors sequesters lymphocyte subsets in peripheral lymphoid organs, preventing their trafficking to inflamed tissue sites, modulating immunity. Targeting S1P receptors for treating autoimmune disease has been established in clinical studies with the non‐selective S1P modulator, FTY720 (fingolimod, Gilenya™). The purpose of this study was to assess RPC1063 for its therapeutic utility in autoimmune diseases. Experimental Approach: The specificity and potency of RPC1063 (ozanimod) was evaluated for all five S1P receptors, and its effect on cell surface S1P 1 receptor expression, was characterized in vitro . The oral pharmacokinetic (PK) parameters and pharmacodynamic effects were established in rodents, and its activity in three models of autoimmune disease (experimental autoimmune encephalitis, 2,4,6‐trinitrobenzenesulfonic acid colitis and CD4 + CD45RB hi T cell adoptive transfer colitis) was assessed. Key Results: RPC1063 was specific for S1P 1 and S1P 5 receptors, induced S1P 1 receptor internalization and induced a reversible reduction in circulating B and CCR7 + T lymphocytes in vivo . RPC1063 showed high oral bioavailability and volume of distribution, and a circulatory half‐life that supports once daily dosing. Oral RPC1063 reduced inflammation and disease parameters in all three autoimmune disease models. Conclusions and Implications: S1P receptor selectivity, favourable PK properties and efficacy in three distinct disease models supports the clinical development of RPC1063 for the treatment of relapsing multiple sclerosis and inflammatory bowel disease, differentiates RPC1063 from other S1P receptor agonists, and could result in improved safety outcomes in the clinic.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Animal research: Reporting in vivo experiments: The ARRIVE guidelines
Kilkenny, C., Browne, W., Cuthill, I. C., Emerson, M., & Altman, D. G. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00872.x · Cited by 3,625
Alteration of Lymphocyte Trafficking by Sphingosine-1-Phosphate Receptor Agonists
Mandala, S., Hajdu, R., Bergstrom, J., Quackenbush, E., Xie, J., Milligan, J., Thornton, R., Shei, G.-J., Card, D., Keohane, C., et al. (2002) · Science · doi:10.1126/science.1070238 · Cited by 1,690
Self-citationMcGrath, J. C., & Lilley, E. (2015) · British Journal of Pharmacology · doi:10.1111/bph.12955 · Cited by 1,321
Liu, Y., Wada, R., Yamashita, T., Mi, Y., Deng, C.-X., Hobson, J. P., Rosenfeldt, H. M., Nava, V. E., Chae, S.-S., Lee, M.-J., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10905 · Cited by 1,149
Experimental design and analysis and their reporting: new guidance for publication in BJP
Curtis, M. J., Bond, R. A., Spina, D., Ahluwalia, A., Alexander, S. P. A., Giembycz, M. A., Gilchrist, A., Hoyer, D., Insel, P. A., Izzo, A. A., et al. (2015) · British Journal of Pharmacology · doi:10.1111/bph.12856 · Cited by 1,033
The Concise Guide to PHARMACOLOGY 2015/16: G protein‐coupled receptors
Alexander, S. P., Davenport, A. P., Kelly, E., Marrion, N., Peters, J. A., Benson, H. E., Faccenda, E., Pawson, A. J., Sharman, J. L., Southan, C., et al. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13348 · Cited by 851
Pawson, A. J., Sharman, J. L., Benson, H. E., Faccenda, E., Alexander, S. P. H., Buneman, O. P., Davenport, A. P., McGrath, J. C., Peters, J. A., Southan, C., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1143 · Cited by 849
The Concise Guide to PHARMACOLOGY 2015/16: Enzymes
Alexander, S. P., Fabbro, D., Kelly, E., Marrion, N., Peters, J. A., Benson, H. E., Faccenda, E., Pawson, A. J., Sharman, J. L., Southan, C., et al. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13354 · Cited by 604
Choi, J. W., Gardell, S. E., Herr, D. R., Rivera, R., Lee, C.-W., Noguchi, K., Teo, S. T., Yung, Y. C., Lu, M., Kennedy, G., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1014154108 · Cited by 581
Brinkmann, V. (2007) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.04.006 · Cited by 528
Clinical targeting of the TNF and TNFR superfamilies
Croft, M., Benedict, C. A., & Ware, C. F. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd3930 · Cited by 456
Soler, D., Chapman, T., Yang, L.-L., Wyant, T., Egan, R., & Fedyk, E. R. (2009) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.153973 · Cited by 456
Pham, T. H. M., Okada, T., Matloubian, M., Lo, C. G., & Cyster, J. G. (2008) · Immunity · doi:10.1016/j.immuni.2007.11.017 · Cited by 427
Oo, M. L., Thangada, S., Wu, M.-T., Liu, C. H., Macdonald, T. L., Lynch, K. R., Lin, C.-Y., & Hla, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610318200 · Cited by 405
G-protein-coupled receptor S1P1 acts within endothelial cells to regulate vascular maturation
Allende, M. L., Yamashita, T., & Proia, R. L. (2003) · Blood · doi:10.1182/blood-2003-02-0460 · Cited by 380
Persistent signaling induced by FTY720-phosphate is mediated by internalized S1P1 receptors
Mullershausen, F., Zecri, F., Cetin, C., Billich, A., Guerini, D., & Seuwen, K. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.173 · Cited by 370
FTY720 therapy exerts differential effects on T cell subsets in multiple sclerosis
Mehling, M., Brinkmann, V., Antel, J., Bar-Or, A., Goebels, N., Vedrine, C., Kristofic, C., Kuhle, J., Lindberg, R. L. P., & Kappos, L. (2008) · Neurology · doi:10.1212/01.wnl.0000327609.57688.ea · Cited by 345
Groves, A., Kihara, Y., & Chun, J. (2013) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2013.02.011 · Cited by 314
Gergely, P., Nuesslein‐Hildesheim, B., Guerini, D., Brinkmann, V, Traebert, M., Bruns, C., Pan, S., Gray, N., Hinterding, K., Cooke, N., et al. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.02061.x · Cited by 305
Idzko, M., Hammad, H., Nimwegen, M. V., Kool, M., Müller, T., Soullié, T., Willart, M. A. M., Hijdra, D., Hoogsteden, H. C., & Lambrecht, B. N. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28295 · Cited by 258
FTY720 modulates human oligodendrocyte progenitor process extension and survival
Miron, V. E., Jung, C. G., Kim, H. J., Kennedy, T. E., Soliven, B., & Antel, J. P. (2008) · Annals of Neurology · doi:10.1002/ana.21227 · Cited by 255
Hasegawa, Y., Suzuki, H., Sozen, T., Rolland, W., & Zhang, J. H. (2010) · Stroke · doi:10.1161/strokeaha.109.568899 · Cited by 242
Jo, E., Sanna, M. G., Gonzalez-Cabrera, P. J., Thangada, S., Tigyi, G., Osborne, D. A., Hla, T., Parrill, A. L., & Rosen, H. (2005) · Chemistry & Biology · doi:10.1016/j.chembiol.2005.04.019 · Cited by 240
Self-citationSelmaj, K., Li, D. K., Hartung, H.-P., Hemmer, B., Kappos, L., Freedman, M. S., Stüve, O., Rieckmann, P., Montalban, X., Ziemssen, T., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70102-9 · Cited by 234
Kataoka, H., Sugahara, K., Shimano, K., Teshima, K., Koyama, M., Fukunari, A., & Chiba, K. (2005) · PubMed · Cited by 216
The Immunomodulator FTY720 Has a Direct Cytoprotective Effect in Oligodendrocyte Progenitors
Coelho, R. P., Payne, S. G., Bittman, R., Spiegel, S., & Sato-Bigbee, C. (2007) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.123927 · Cited by 175
Thangada, S., Khanna, K. M., Blaho, V. A., Oo, M. L., Im, D.-S., Guo, C., Lefrancois, L., & Hla, T. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20091343 · Cited by 172
Daniel, C., Sartory, N., Zahn, N., Geisslinger, G., Radeke, H. H., & Stein, J. M. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.4.2458 · Cited by 165
The Concise Guide to PHARMACOLOGY 2015/16: Catalytic receptors
Alexander, S. P., Fabbro, D., Kelly, E., Marrion, N., Peters, J. A., Benson, H. E., Faccenda, E., Pawson, A. J., Sharman, J. L., Southan, C., et al. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13353 · Cited by 159
Balatoni, B., Storch, M. K., Swoboda, E.-M., Schönborn, V., Koziel, A., Lambrou, G. N., Hiestand, P. C., Weissert, R., & Foster, C. A. (2007) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2007.06.023 · Cited by 158
Dev, K. K., Müllershausen, F., Mattes, H., Kuhn, R. R., Bilbe, G., Hoyer, D., & Mir, A. K. (2007) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.08.005 · Cited by 157
Vaclavkova, A., Chimenti, S., Arenberger, P., Holló, P., Sator, P.-G., Burcklen, M., Stefani, M., & D’Ambrosio, D. (2014) · The Lancet · doi:10.1016/s0140-6736(14)60803-5 · Cited by 154
Oral ponesimod in relapsing-remitting multiple sclerosis: a randomised phase II trial
Olsson, T. P., Boster, A. L., Fernández, Ó., Freedman, M. S., Pozzilli, C., Bach, D., Berkani, O., Mueller, M. S., Tv, S., Radue, E. W., et al. (2014) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2013-307282 · Cited by 153
Phosphorylated FTY720 promotes astrocyte migration through sphingosine-1-phosphate receptors
Müllershausen, F., Craveiro, L. M., Shin, Y., Cortés-Cros, M., Bassilana, F., Osinde, M., Wishart, W. L., Guerini, D., Thallmair, M., Schwab, M. E., et al. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04629.x · Cited by 142
Gonzalez‐Cabrera, P. J., Jo, E., Sanna, M., Brown, S. J., Leaf, N. B., Marsolais, D., Schaeffer, M., Chapman, J. V., Cameron, M. D., Guerrero, M., et al. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.049783 · Cited by 129
Self-citationvan Doorn, R., Nijland, P. G., Dekker, N., Witte, M. E., Pinheiro, M. A. L., Hof, B. V. H., Kooij, G., Reijerkerk, A., Dijkstra, C. D., van der Valk, P., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-1014-4 · Cited by 126
Effects of FTY720 in MRL-lpr/lpr mice: therapeutic potential in systemic lupus erythematosus.
Okazaki, H., Hirata, D., Kamimura, T., Sato, H., Iwamoto, M., Yoshio, T., Masuyama, J., Fujimura, A., Kobayashi, E., Kano, S., et al. (2002) · PubMed · Cited by 124
Phosphorylated FTY720 stimulates ERK phosphorylation in astrocytes via S1P receptors
Osinde, M., Müllershausen, F., & Dev, K. K. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.11.010 · Cited by 112
Song, J., Matsuda, C., Kai, Y., Nishida, T., Nakajima, K., Mizushima, T., Kinoshita, M., Yasue, T., Sawa, Y., & Ito, T. (2007) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.119172 · Cited by 98
Danese, S., & Panés, J. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.08.044 · Cited by 98
The S1P receptor modulator FTY720 prevents the development of experimental colitis in mice
Deguchi, Y., Andoh, A., Yagi, Y., Bamba, S., Inatomi, O., Tsujikawa, T., & Fujiyama, Y. (2006) · Oncology Reports · doi:10.3892/or.16.4.699 · Cited by 91
Keller, C., Rivera-Gil, P., Tölle, M., van der Giet, M., Chun, J. J. M., Radeke, H. H., Schäfer‐Korting, M., & Kleuser, B. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.060485 · Cited by 88
T cell-induced inflammation of the small and large intestine in immunodeficient mice
Ostanin, D. V., Pavlick, K. P., Bharwani, S., D’Souza, D., Furr, K. L., Brown, C. M., & Grisham, M. B. (2005) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00214.2005 · Cited by 84
Single‐dose FTY720 pharmacokinetics, food effect, and pharmacological responses in healthy subjects
Kovarik, J. M., Schmouder, R., Barilla, D., Wang, Y., & Kraus, G. (2004) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2003.02065.x · Cited by 81
Fryer, R. M., Muthukumarana, A. C., Harrison, P. C., Mazurek, S. N., Chen, R. R., Harrington, K. E., Dinallo, R. M., Horan, J. C., Patnaude, L. A., Modis, L. K., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052985 · Cited by 81
Mizushima, T., Ito, T., Kishi, D., Kai, Y., Tamagawa, H., Nezu, R., Kiyono, H., & Matsuda, H. (2004) · Inflammatory Bowel Diseases · doi:10.1097/00054725-200405000-00002 · Cited by 74
FTY720 suppresses CD4+CD44highCD62L− effector memory T cell-mediated colitis
Fujii, R., Kanai∥, T., Nemoto, Y., Makita, S., Oshima, S., Okamoto, R., Tsuchiya, K., Totsuka, T., & Watanabe, M. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00496.2005 · Cited by 66
Methods of Inducing Inflammatory Bowel Disease in Mice
Maxwell, J. R., Brown, W. A., Smith, C. S., Byrne, F. R., & Viney, J. L. (2009) · Current Protocols in Pharmacology · doi:10.1002/0471141755.ph0558s47 · Cited by 65
Xin, C., Ren, S., Eberhardt, W., Pfeilschifter, J. M., & Huwiler, A. (2005) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706452 · Cited by 64
Holm, T. L., Poulsen, S. S., Markholst, H., & Reedtz-Runge, S. L. (2012) · International Journal of Inflammation · doi:10.1155/2012/412178 · Cited by 43
Wang, F., Tan, W., Guo, D., & He, S. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.07.029 · Cited by 43
Sphingosine-1 Phosphate and Central Nervous System
Martinꝉ, R., & Sospedra, M. (2014) · Current topics in microbiology and immunology · doi:10.1007/978-3-319-05879-5_7 · Cited by 38
Galicia, G., Pikor, N. B., Schwartz, J. A., Rojas, O. L., Jian, A., deLuca, L. S., Ostrowski, M., Nuesslein‐Hildesheim, B., & Gommerman, J. L. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1102261 · Cited by 38
Krösser, S., Wolna, P., Fischer, T. Z., Boschert, U., Stoltz, R. R., Zhou, M., & Darpö, B. (2015) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.513 · Cited by 29
Comı, G., Cohen, J. A., Arnold, D. L., Bar‐Or, A., Gujrathi, S., Hartung, J. P., Olson, A. D., Cravets, M. W., Frohna, P., & Selmaj, K. W. (2015) · Neurology · doi:10.1212/wnl.84.14_supplement.p7.198 · Cited by 5
Cited by
Comi, G., Kappos, L., Selmaj, K. W., Bar-Or, A., Arnold, D. L., Steinman, L., Hartung, H.-P., Montalban, X., Kubala Havrdová, E., Cree, B. A. C., et al. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30239-x · Cited by 285
Targeting sphingosine-1-phosphate signaling in immune-mediated diseases: beyond multiple sclerosis
Pérez-Jeldres, T., Alvarez-Lobos, M., & Rivera-Nieves, J. (2021) · Drugs · doi:10.1007/s40265-021-01528-8 · Cited by 197
Next generation of small molecules in inflammatory bowel disease
Olivera, P., Danese, S., & Peyrin-Biroulet, L. (2017) · Gut · doi:10.1136/gutjnl-2016-312912 · Cited by 154
Pérez-Jeldres, T., Tyler, C. J., Boyer, J. D., Karuppuchamy, T., Yarur, A., Giles, D. A., Yeasmin, S., Lundborg, L., Sandborn, W. J., Patel, D. R., et al. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00212 · Cited by 126
Structural basis for receptor selectivity and inverse agonism in S1P5 receptors
Lyapina, E., Marin, E., Gusach, A., Orekhov, P., Gerasimov, A., Luginina, A., Vakhrameev, D., Ergasheva, M., Kovaleva, M., Khusainov, G., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32447-1 · Cited by 26
Metadata
- Authors
- Scott, F. L., Clemons, B., Brooks, J., Brahmachary, E., Powell, R., Dedman, H., Desale, H. G., Timony, G. A., Martinborough, E., Rosen, H., Roberts, E., Boehm, M. F., & Peach, R. J.
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2016-04-28
- Volume
- 173
- Issue
- 11
- Pages
- 1778-1792
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- OpenAlex
- W2299774205
- Cited by
- 308
- References
- 55
- FWCI
- 9.48
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
