Journal ArticleDOI
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,Shreeram Aradhye,Pascale Burtin +7 more
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TLDR
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.Abstract:
The discovery of fingolimod (FTY720/Gilenya; Novartis), an orally active immunomodulatory drug, has opened up new approaches to the treatment of multiple sclerosis, the most common inflammatory disorder of the central nervous system. Elucidation of the effects of fingolimod--mediated by the modulation of sphingosine 1-phosphate (S1P) receptors--has indicated that its therapeutic activity could be due to regulation of the migration of selected lymphocyte subsets into the central nervous system and direct effects on neural cells, particularly astrocytes. An improved understanding of the biology of S1P receptors has also been gained. This article describes the discovery and development of fingolimod, 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.read more
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Natural Products As Sources of New Drugs over the 30 Years from 1981 to 2010
David J. Newman,Gordon M. Cragg +1 more
TL;DR: This review is an updated and expanded version of the three prior reviews and adds a new designation, "natural product botanical" or "NB", to cover those botanical "defined mixtures" that have now been recognized as drug entities by the FDA and similar organizations.
Journal ArticleDOI
Drug repurposing: progress, challenges and recommendations
Sudeep Pushpakom,Francesco Iorio,Patrick A. Eyers,K. Jane Escott,Shirley Hopper,Andrew D. Wells,Andrew J. Doig,Tim Guilliams,Joanna Latimer,Christine J. McNamee,Alan Norris,Philippe Sanseau,David Cavalla,Munir Pirmohamed +13 more
TL;DR: Approaches used for drug repurposing (also known as drug repositioning) are presented, the challenges faced by the repurpose community are discussed, and innovative ways by which these challenges could be addressed are recommended to help realize the full potential of drugRepurposing.
Journal ArticleDOI
Next Generation of Fluorine-Containing Pharmaceuticals, Compounds Currently in Phase II–III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas
Yu Zhou,Jiang Wang,Zhanni Gu,Shuni Wang,Wei Zhu,José Luis Aceña,Vadim A. Soloshonok,Kunisuke Izawa,Hong Liu +8 more
TL;DR: Compounds Currently in Phase II−III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas is presented.
Journal ArticleDOI
Trends in GPCR drug discovery: new agents, targets and indications
Alexander S. Hauser,Misty M. Attwood,Mathias Rask-Andersen,Helgi B. Schiöth,David E. Gloriam +4 more
TL;DR: An up-to-date analysis of all GPCR drugs and agents in clinical trials is reported, which reveals current trends across molecule types, drug targets and therapeutic indications, including showing that 475 drugs act at 108 unique GPCRs.
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Sphingolipid metabolites in inflammatory disease
Michael Maceyka,Sarah Spiegel +1 more
TL;DR: The knowledge gained in this emerging field of sphingolipid metabolism will aid in the development of new therapeutic options for inflammatory disorders.
References
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Journal ArticleDOI
Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
TL;DR: It is shown that expression of CCR7, a chemokine receptor that controls homing to secondary lymphoid organs, divides human memory T cells into two functionally distinct subsets, which are named central memory (TCM) and effector memory (TEM).
Journal ArticleDOI
A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis
Chris H. Polman,Eva Havrdova,Michael Hutchinson,Ludwig Kappos,David Miller,J. Theodore Phillips,Fred D. Lublin,Gavin Giovannoni,A Wajgt,Martin Toal,F Lynn,Michael Panzara,Alfred Sandrock +12 more
TL;DR: Natalizumab reduced the risk of the sustained progression of disability and the rate of clinical relapse in patients with relapsing multiple sclerosis and hold promise as an effective treatment for relapsed multiple sclerosis.
Journal ArticleDOI
Central Memory and Effector Memory T Cell Subsets: Function, Generation, and Maintenance
TL;DR: This review addresses the heterogeneity of TCM and TEM, their differentiation stages, and the current models for their generation and maintenance in humans and mice.
Journal ArticleDOI
Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis
Lawrence Jacobs,Diane Cookfair,Richard A. Rudick,Robert M. Herndon,John R. Richert,Andres M. Salazar,J. S. Fischer,Donald E. Goodkin,Carl V. Granger,Jack H. Simon,John J. Alam,David M. Bartoszak,Dennis Bourdette,Jonathan Braiman,Carol M. Brownscheidle,Michael E. Coats,Stanley Cohan,David S. Dougherty,R. P. Kinkel,Michele Mass,Frederick Munschauer,Roger L. Priore,Patrick M. Pullicino,Barbara J. Scherokman,Bianca Weinstock-Guttman,Ruth H. Whitham +25 more
TL;DR: Interferon beta‐ la had a significant beneficial impact in relapsing multiple sclerosis patients by reducing the accumulation of permanent physical disability, exacerbation frequency, and disease activity measured by gadolinium‐enhanced lesions on brain magnetic resonance images.
Journal ArticleDOI
Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1
Mehrdad Matloubian,Charles G. Lo,Guy Cinamon,Matthew J. Lesneski,Ying Xu,Volker Brinkmann,Maria L. Allende,Richard L. Proia,Jason G. Cyster +8 more
TL;DR: It is established that S1P1 is essential for lymphocyte recirculation and that it regulates egress from both thymus and peripheral lymphoid organs.