Review
Pharmacology & Pharmacy
Gerhild van Echten-Deckert
Summary: Lipids are essential components of the CNS, and sphingolipids, a type of lipid, are highly concentrated in the brain. Sphingosine 1-phosphate (S1P), derived from membrane sphingolipids, has complex effects on the brain, which can be both beneficial and detrimental. However, the role of S1P in brain development and various brain pathologies is still controversial.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Immunology
Zu -An Shi, Cheng-Xiu Yu, Zhi-Chao Wu, Chang -Lin Chen, Fa -Ping Tu, Yong Wan
Summary: The study investigated the protective effect of Fingolimod in a rat model of acute lung injury induced by LPS, showing inhibition of NF-kappa B activation, reduction of inflammatory cytokines, and improvement in lung tissue injury. These results suggest a promising therapeutic potential for Fingolimod in LPS-induced ALI by regulating the inflammatory pathway and barrier dysfunction of alveolar capillaries.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Review
Cell Biology
Gary Alvarez Bravo, Rene Robles Cedeno, Marc Puig Casadevall, Lluis Ramio-Torrenta
Summary: Sphingosine-1-phosphate (S1P) and S1P receptors (S1PR) play an important role in the immune system, especially in relation to multiple sclerosis. Modulation of S1P has potential significance for treating autoimmune disorders.
Article
Pharmacology & Pharmacy
Julie Selkirk, Kevin C. Dines, Yingzhuo Grace Yan, Nathan Ching, Deepak Dalvie, Shameek Biswas, Andrea Bortolato, Jeffrey M. Schkeryantz, Carlos Lopez, Iliana Ruiz, Richard Hargreaves
Summary: Ozanimod, a selective modulator of human sphingisone 1phosphate receptor subtypes 1 and 5 (S1P(1/5)), displays reduced potency for rodent and dog S1P(5) compared with human, resulting from a mutation at position 120. In mouse models of multiple sclerosis, S1P(1) activation is neuroprotective, but S1P(5) may be necessary for remyelination.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2021)
Article
Neurosciences
Yasuyuki Kihara, Yunjiao Zhu, Deepa Jonnalagadda, William Romanow, Carter Palmer, Benjamin Siddoway, Richard Rivera, Ranjan Dutta, Bruce D. Trapp, Jerold Chun
Summary: This study used snRNA-seq to analyze 33,197 nuclei from 8 normal-appearing MS brains, revealing cell type-specific changes between RRMS and SPMS. Interestingly, the downregulation of astrocytic sphingosine kinases in SPMS brains could affect the activity of the MS drug fingolimod. These findings provide an initial resource for studying non-lesioned RRMS and SPMS brain cell units.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Pharmacology & Pharmacy
Sekhar Surapaneni, Usha Yerramilli, April Bai, Deepak Dalvie, Jennifer Brooks, Xiaomin Wang, Julie Selkirk, Yingzhuo Grace Yan, Peijin Zhang, Richard Hargreaves, Gondi Kumar, Maria Palmisano, Jonathan Q. Tran
Summary: Absorption, metabolism, and excretion of ozanimod in humans were characterized, and the enzymes involved in complex metabolism were elucidated. Disproportionate metabolites were identified, and the activity of these metabolites was determined.
DRUG METABOLISM AND DISPOSITION
(2021)
Article
Cell Biology
Chiara Donati, Francesca Cencetti, Caterina Bernacchioni, Valentina Vannuzzi, Paola Bruni
Summary: Fibrosis is a devastating multifaceted disease that can be treated by regulating the S1P signaling pathway and its cross-talk with other profibrotic mediators.
CELLULAR SIGNALLING
(2021)
Article
Biochemistry & Molecular Biology
Sun Jun Park, Jushin Kim, Jaehwan Kim, Yoowon Kim, Elijah Hwejin Lee, Hyeon Jeong Kim, Siwon Kim, Byungeun Kim, Rium Kim, Ji Won Choi, Jong-Hyun Park, Ki Duk Park
Summary: Sphingosine-1-phosphate-1 (S1P(1)) receptor agonists are drugs commonly used for treating multiple sclerosis. Researchers synthesized a natural product called serinolamide A and found that it functioned as an antagonist to S1P(1) receptor agonists. They also discovered that compound 19, a derivative of serinolamide, had superior agonistic effects and effectively inhibited lymphocyte outflow.
Article
Gastroenterology & Hepatology
Jie Wang, Idan Goren, Bo Yang, Sinan Lin, Jiannan Li, Michael Elias, Claudio Fiocchi, Florian Rieder
Summary: S1P receptor modulators are a novel, promising, and safe strategy for the treatment of IBD, with several potential candidates showing positive results in clinical trials.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Clinical Neurology
David Croteau, Anne Tobenkin, Allen Brinker, Cindy M. Kortepeter
Summary: The study found a potential association between Tumefactive multiple sclerosis (TMS) and the use of fingolimod, suggesting that clinicians should be vigilant for possible occurrences of TMS in patients experiencing severe or atypical MS relapses shortly after initiating or discontinuing fingolimod. Furthermore, the results indicated that the association between fingolimod and TMS may be stronger compared to other disease-modifying therapies.
MULTIPLE SCLEROSIS JOURNAL
(2021)
Review
Pharmacology & Pharmacy
Jerold Chun, Gavin Giovannoni, Samuel F. Hunter
Summary: Lysophospholipids, particularly sphingosine 1-phosphate (S1P), act through G protein-coupled receptors (GPCRs) and have complex effects on physiological and pathophysiological events. S1PR modulators, including fingolimod, siponimod, and ozanimod, have been approved for multiple sclerosis (MS) treatment, with others like ponesimod and etrasimod in clinical development. These modulators show subtype specificity for S1PRs, influencing downstream effects, and can act as both agonists and functional antagonists.
Letter
Clinical Neurology
Catherine Wainwright, Steve Fuller, Victoria Dickinson, Wendy Greenwood
Summary: This study analyzed the content of fingolimod in three FDA approved generic capsule products and found significant variation between manufacturers. One of the products had a fingolimod content of only 76.8% of the approved dose, falling below the FDA acceptance criteria.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2023)
Article
Clinical Neurology
Silvia Delgado, Jeffrey Hernandez, Leticia Tornes, Kottil Rammohan
Summary: In this study, the authors presented six patients with relapsing-remitting MS who experienced an unexpected increase in disease activity after transitioning from fingolimod to DMF. Despite being stable on fingolimod for at least 1 year, all patients experienced relapse with enhancing lesions after switching to DMF. Additional studies are needed to determine the most effective treatment strategy after discontinuing fingolimod.
Article
Clinical Neurology
Fabian Maass, Philipp von Gottberg, Jonas Franz, Christine Stadelmann, Mathias Baehr, Martin S. Weber
Summary: Fingolimod is a highly effective drug for treating RRMS, but immunosuppressive effects can lead to adverse events such as increased cancer risk and opportunistic infections, which should be carefully monitored. In a case presented here, the presence of asymptomatic PML and lung cancer brain metastases suggests possible risks associated with Fingolimod treatment.
FRONTIERS IN NEUROLOGY
(2021)
Article
Chemistry, Organic
Parvin Asadi, Ghadamali Khodarahmi, Amin Rafiee, Mehdi Aliomrani, Farshid Hassanzadeh
Summary: Different heterocyclic entities were designed based on the structure of fingolimod, the first oral drug for multiple sclerosis (MS), and their interactions with S1P(1) and S1P(3) were evaluated. The 4-aminopyridine substituted derivative showed better binding energy with S1P(3) and was able to reduce white blood cells without damaging red blood cells.
POLYCYCLIC AROMATIC COMPOUNDS
(2023)