Preclinical discovery and development of fingolimod for the treatment of multiple sclerosis

Expert Opinion on Drug Discovery
Claudia VolpiUrsula Grohmann

Abstract

Introduction: Fingolimod, the first oral disease-modifying treatment (DMT) in multiple sclerosis (MS), is a sphingosine 1-phosphate receptor (S1PR) ligand. Approved in 2010, fingolimod has been extensively studied and has been credited with several mechanisms of actions that contribute to its efficacy in MS, among which is the regulation of lymphocyte circulation between the central nervous system and the periphery. Concerns about toxicity, off-target effects, and real-life performance have been raised over time in post-marketing studies of such that next-generation sphingosine-1 phosphate receptor ligands are now being developed. Areas covered: Herein, the authors expand upon previous systematic reviews obtained via PubMed and through their expert opinion on fingolimod use in clinical practice. Long-term data including long-term efficacy, safety, tolerability, and management especially within growing DMT options and pre-treatment constellation in MS patients are discussed, together with the results of an increased understanding of the chemistry underlying the structure-activity relationship. Expert opinion: Despite the limitations illustrated in this article, fingolimod still constitutes a paradigm shift in MS treatment. Howev...Continue Reading

References

Jun 15, 1995·Biochemical and Biophysical Research Communications·Y MiyakeT Kawasaki
Oct 25, 1996·Journal of Medicinal Chemistry·T FujitaM Arita
Feb 9, 2000·Trends in Pharmacological Sciences·V BrinkmannL Feng
Sep 28, 2000·The New England Journal of Medicine·J H NoseworthyB G Weinshenker
Dec 1, 2001·Science·T HlaM J Kluk
Apr 23, 2002·The Journal of Biological Chemistry·Volker BrinkmannKevin R Lynch
Apr 23, 2002·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·David MazuraisThierry Calmels
Aug 17, 2002·Current Opinion in Immunology·Volker Brinkmann, Kevin R Lynch
Sep 28, 2002·Transplantation·Michael N TawadrousAntony M Wheatley
Mar 22, 2003·The Journal of Pharmacology and Experimental Therapeutics·Masayuki FujinoXiao-Kang Li
Apr 2, 2003·Cardiovascular Research·Tsukasa OhmoriYukio Ozaki
Sep 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Junsuke IgarashiThomas Michel
Sep 18, 2003·The Journal of Biological Chemistry·Andreas BillichThomas Baumruker
Nov 5, 2003·FEBS Letters·Steven W PaughSarah Spiegel
Jan 13, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Markus H Gräler, Edward J Goetzl
May 4, 2004·Annals of Neurology·Pia KivisäkkRichard M Ransohoff
Jun 16, 2004·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Volker BrinkmannTimothy Hla
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
Jun 11, 2005·The New England Journal of Medicine·Annette Langer-GouldDaniel Pelletier
Jun 11, 2005·The New England Journal of Medicine·B K Kleinschmidt-DeMasters, Kenneth L Tyler
Jun 11, 2005·The New England Journal of Medicine·Gert Van AsschePaul Rutgeerts
Mar 24, 2006·The European Journal of Neuroscience·Nathalie RouachMartine Tencé
Nov 15, 2006·Clinical Transplantation·Klemens BuddeTorsten Böhler
Feb 17, 2007·Expert Opinion on Investigational Drugs·Thomas BaumrukerVolker Brinkmann
Aug 22, 2007·The Journal of Clinical Investigation·Athanasia SkouraTimothy Hla
Aug 23, 2007·Nature Immunology·Henry F McFarland, Roland Martin
Jun 28, 2008·Circulation Research·Bernhard Friedrich PeterSteffen-Sebastian Bolz
Oct 31, 2008·Lancet·Alastair Compston, Alasdair Coles
Mar 17, 2009·Cardiovascular Research·Athanasia Skoura, Timothy Hla
Jan 22, 2010·The New England Journal of Medicine·Ludwig KapposUNKNOWN FREEDOMS Study Group
Jan 22, 2010·The New England Journal of Medicine·Jeffrey A CohenUNKNOWN TRANSFORMS Study Group
May 4, 2010·Neuroscience Letters·Alina KułakowskaRobert Bucki
Dec 24, 2010·Proceedings of the National Academy of Sciences of the United States of America·Ji Woong ChoiJerold Chun

❮ Previous
Next ❯

Citations

Aug 14, 2020·PLoS Pathogens·Rachel S ResopAlberto Bosque
Sep 12, 2020·Neuromolecular Medicine·Bhakta Prasad Gaire, Ji Woong Choi
Apr 21, 2020·Current Neuropharmacology·Yam Nath PaudelMohd Farooq Shaikh
Aug 8, 2021·International Journal of Molecular Sciences·Bhakta Prasad Gaire, Ji-Woong Choi

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Clinical Pharmacokinetics
Olivier J DavidRobert L Schmouder
Expert Opinion on Drug Metabolism & Toxicology
Radu Tanasescu, Cris S Constantinescu
Clinical Neurology and Neurosurgery
Katja Thomas, Tjalf Ziemssen
© 2021 Meta ULC. All rights reserved