Ponesimod, a selective S1P1 receptor modulator: a potential treatment for multiple sclerosis and other immune-mediated diseases

Therapeutic Advances in Chronic Disease
Daniele D'AmbrosioJoerg Prinz

Abstract

The first oral treatment for relapsing multiple sclerosis, the nonselective sphingosine-1-phosphate receptor (S1PR) modulator fingolimod, led to identification of a pivotal role of sphingosine-1-phosphate and one of its five known receptors, S1P1R, in regulation of lymphocyte trafficking in multiple sclerosis. Modulation of S1P3R, initially thought to cause some of fingolimod's side effects, prompted the search for novel compounds with high selectivity for S1P1R. Ponesimod is an orally active, selective S1P1R modulator that causes dose-dependent sequestration of lymphocytes in lymphoid organs. In contrast to the long half-life/slow elimination of fingolimod, ponesimod is eliminated within 1 week of discontinuation and its pharmacological effects are rapidly reversible. Clinical data in multiple sclerosis have shown a dose-dependent therapeutic effect of ponesimod and defined 20 mg as a daily dose with desired efficacy, and acceptable safety and tolerability. Phase II clinical data have also shown therapeutic efficacy of ponesimod in psoriasis. These findings have increased our understanding of psoriasis pathogenesis and suggest clinical utility of S1P1R modulation for treatment of various immune-mediated disorders. A gradual do...Continue Reading

References

Jun 5, 2003·European Journal of Pharmacology·Salvatore SalomoneChristian Waeber
Nov 30, 2004·Cellular Signalling·Kenneth R WattersonSarah Spiegel
Feb 15, 2005·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Lev KoyrakhKevin Wickman
May 6, 2006·American Journal of Physiology. Gastrointestinal and Liver Physiology·Wenhui HuKarnam S Murthy
May 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laura DiluvioJoerg C Prinz
Sep 15, 2006·The New England Journal of Medicine·Ludwig KapposUNKNOWN FTY720 D2201 Study Group
Sep 23, 2006·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·John N LorenzA John MacLennan
Feb 7, 2007·Current Opinion in Pharmacology·Stephan L M Peters, Astrid E Alewijnse
Dec 9, 2008·Nature Immunology·Irina L GrigorovaJason G Cyster
Dec 17, 2008·Hematology·Stephanie J Lee, Mary E D Flowers
Jan 22, 2010·The New England Journal of Medicine·Ludwig KapposUNKNOWN FREEDOMS Study Group
May 8, 2010·Journal of Medicinal Chemistry·Martin H BolliThomas Weller
Aug 6, 2010·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Daniel WolffErnst Holler
Dec 24, 2010·Proceedings of the National Academy of Sciences of the United States of America·Ji Woong ChoiJerold Chun
Feb 26, 2011·Neurology·Daniel D PinschewerDoron Merkler
Feb 25, 2011·The Journal of Pharmacology and Experimental Therapeutics·Luca PialiMartine Clozel
Oct 14, 2011·The New England Journal of Medicine·Paul O'ConnorUNKNOWN TEMSO Trial Group
Nov 9, 2011·The Korean Journal of Hematology·Paul J MartinMary E D Flowers
Dec 14, 2011·Annual Review of Immunology·Jason G Cyster, Susan R Schwab
Apr 19, 2013·British Journal of Clinical Pharmacology·Patrick BrossardJasper Dingemanse
Jul 16, 2013·Journal of Neurology·Paul W O'ConnorLudwig Kappos
Sep 3, 2013·Therapeutic Advances in Chronic Disease·Mark S Freedman
Dec 24, 2013·European Journal of Clinical Pharmacology·Maribel ReyesJasper Dingemanse
Feb 15, 2014·Multiple Sclerosis : Clinical and Laboratory Research·Masakazu NakamuraTakashi Yamamura
Mar 25, 2014·Journal of Neurology, Neurosurgery, and Psychiatry·Tomas OlssonMaria Melanson
Jun 16, 2014·Journal of Pharmacokinetics and Pharmacodynamics·Andreas KrauseJasper Dingemanse
Jul 22, 2014·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·M HochJ Dingemanse
Sep 5, 2014·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Maribel ReyesJasper Dingemanse
Oct 8, 2014·Basic & Clinical Pharmacology & Toxicology·Matthias HochJasper Dingemanse
Dec 3, 2014·American Heart Journal·John CammVolker Brinkmann
Dec 19, 2014·Immunopharmacology and Immunotoxicology·Daniele D'AmbrosioJasper Dingemanse
Jan 13, 2015·F1000prime Reports·Pedro J Gonzalez-CabreraHugh Rosen
Jan 23, 2015·Journal of Clinical Pharmacology·Michael W ScherzJasper Dingemanse

❮ Previous
Next ❯

Citations

Dec 31, 2016·Biomolecules & Therapeutics·Soo-Jin Park, Dong-Soon Im
Jun 18, 2017·Science China. Life Sciences·Zuoquan XieMeiyu Geng
Jun 20, 2017·Journal of Controlled Release : Official Journal of the Controlled Release Society·Mikhail DurymanovJoshua Reineke
Mar 13, 2018·Expert Opinion on Pharmacotherapy·Paulus S Rommer, Uwe K Zettl
Dec 12, 2017·Pharmacology Research & Perspectives·Luca PialiOliver Nayler
Jun 28, 2017·Journal of the European Academy of Dermatology and Venereology : JEADV·G GirolomoniJ C Prinz
Mar 11, 2020·Journal of Cellular and Molecular Medicine·Lincheng ZhangYueqi Chen
Aug 19, 2020·Expert Opinion on Pharmacotherapy·Elisa Baldin, Alessandra Lugaresi
Jan 16, 2019·Reviews in the Neurosciences·Tomasz Grzegorski, Jacek Losy
Aug 21, 2019·Frontiers in Pharmacology·Sara GrassiPaola Giussani
Jan 6, 2017·Advances in Therapy·Roberta GualtierottiGiovanni Marfia
Aug 31, 2016·Experimental Dermatology·Markus ThiemeChristian D Sadik
May 11, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Ranjeet Prasad DashNuggehally R Srinivas
Nov 20, 2016·Gut·Pablo OliveraLaurent Peyrin-Biroulet
Oct 18, 2020·International Journal of Molecular Sciences·Alessandra RoggeriTim Vanmierlo
Dec 22, 2020·Antiviral Research·Yuzy FauzyahYoshiharu Matsuura
Oct 15, 2020·International Journal of Molecular Sciences·Michio Tokuyama, Tomotaka Mabuchi
Apr 3, 2021·CNS Drugs·Reshmi RoyMark S Freedman
Apr 27, 2021·Pharmacology & Therapeutics·Shuai ShaoTiantai Zhang
Jul 31, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Alexander Kalinkovich, Gregory Livshits
Aug 10, 2021·Cell Biochemistry and Biophysics·Jeffrey R Jacobson
Mar 12, 2019·Journal of Chemical Information and Modeling·Yonghui ChenXiaojian Wang

❮ Previous
Next ❯

Methods Mentioned

BETA
contraception

Clinical Trials Mentioned

NCT00852670
NCT01208090
NCT01006265
NCT01093326
NCT02425644
NCT02461134

Software Mentioned

OPTIMUM

Related Concepts

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

© 2022 Meta ULC. All rights reserved