Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis
- V. Brinkmann, A. Billich, P. Burtin
- BiologyNature reviews. Drug discovery
- 1 November 2010
The discovery and development of fingolimod is described, which was approved by the US Food and Drug Administration in September 2010 as a first-line treatment for relapsing forms of multiple sclerosis, thereby becoming the first oral disease-modifying therapy to be approved for multiple sclerosis in the United States.
Phosphorylation of the Immunomodulatory Drug FTY720 by Sphingosine Kinases*
- A. Billich, F. Bornancin, P. Dévay, D. Mechtcheriakova, N. Urtz, T. Baumruker
- Biology, ChemistryJournal of Biological Chemistry
- 28 November 2003
It is found that, while FTY720 is also phosphorylated by human SPHK1, the human type 2 isoform phosphorylates the drug 30-fold more efficiently, because of a lower Km of FTY 720 for SPHK2.
Brain Penetration of the Oral Immunomodulatory Drug FTY720 and Its Phosphorylation in the Central Nervous System during Experimental Autoimmune Encephalomyelitis: Consequences for Mode of Action in…
- C. A. Foster, L. Howard, A. Billich
- Biology, MedicineJournal of Pharmacology and Experimental…
- 1 November 2007
It is shown that FTY720 localizes to the CNS white matter, preferentially along myelin sheaths, and is likely due to a culmination of mechanisms involving reduction of autoreactive T cells, neuroprotective influence of FTY 720-P in the CNS, and inhibition of inflammatory mediators in the brain.
Persistent signaling induced by FTY720-phosphate is mediated by internalized S1P1 receptors.
- F. Mullershausen, F. Zécri, Cihan Çeti̇n, A. Billich, D. Guerini, K. Seuwen
- BiologyNature Chemical Biology
- 1 June 2009
It is demonstrated that persistent signaling translates into an increased chemokinetic migration of primary human umbilical vein endothelial cells, which suggests persistent agonism as a crucial parameter in the mechanism of action of FTY720.
Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720.
- B. Zemann, B. Kinzel, A. Billich
- BiologyBlood
- 15 February 2006
The generation of sphingosine kinase 2 (SPHK2) knockout mice is reported on and it is demonstrated that this enzyme is essential for FTY720 phosphate formation in vivo, indicating that SPHK2 is constantly required to maintain FTY 720 phosphate levels in vivo.
PIKfyve, a class III PI kinase, is the target of the small molecular IL-12/IL-23 inhibitor apilimod and a player in Toll-like receptor signaling.
- Xinming Cai, Yongyao Xu, Qian Huang
- BiologyChemistry and Biology
- 25 July 2013
A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis
- Lin Zhang, M. Orban, S. Massberg
- BiologyJournal of Experimental Medicine
- 19 November 2012
Sphingosine 1-phosphate guides the elongation of megakaryocytic proplatelet extensions and triggers their shedding.
Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis
- V. Brinkmann, A. Billich, P. Burtin
- ChemistryNature reviews. Drug discovery
- 2010
Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis Volker Brinkmann, Andreas Billich, Thomas Baumruker, Peter Heining, Robert Schmouder, Gordon Francis,…
Second generation S1P pathway modulators: research strategies and clinical developments.
- M. Bigaud, D. Guerini, A. Billich, F. Bassilana, V. Brinkmann
- BiologyBiochimica et Biophysica Acta
- 1 May 2014
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