Preparation of antibodies against a novel immunosuppressant, FTY720, and development of an enzyme immunoassay for FTY720

Matsumoto, Namiko; Kohno, Takeyuki; Uchida, Shuji; Shimizu, Takaaki; Kusumoto, Haruko; Hirose, Ryoji; Yanada, Kazuo; Kurio, Wasako; Yamaguchi, S.; Watabe, Kazuhito; Fujita, Tetsuro

doi:10.1016/j.bmc.2006.01.071

Cited by 6 publications

(4 citation statements)

References 28 publications

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“…213 Recent studies214 have shown that the ( S )‐enantiomer of FTY720‐ O ‐phosphate shows higher affinity than the ( R )‐enantiomer towards the S1P receptors, in contraposition to previous results 212. 215 Very recently, an azide derivative of FTY720 has been described as the first photoactivatable analogue of this ligand216 and monoclonal antibodies against FTY720, together with a competitive enzyme immunoassay, have been developed 217…”

Section: Structural Modifications Of Sphingolipidsmentioning

confidence: 97%

Chemical Tools to Investigate Sphingolipid Metabolism and Functions

et al. 2007

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Sphingolipids comprise an important group of biomolecules, some of which have been shown to play important roles in the regulation of many cell functions. From a structural standpoint, they all share a long 2-amino-1,3-diol chain, which can be either saturated (sphinganine), hydroxylated at C4 (phytosphingosine), or unsaturated at C4 (sphingosine) as in most mammalian cells. N-acylation of sphingosine leads to ceramide, a key intermediate in sphingolipid metabolism that can be enzymatically modified at the C1-OH position to other biologically important sphingolipids, such as sphingomyelin or glycosphingolipids. In addition, both ceramide and sphingosine can be phosphorylated at C1-OH to give ceramide-1-phosphate and sphingosine-1-phosphate, respectively. To better understand the biological and biophysical roles of sphingolipids, many efforts have been made to design synthetic analogues as chemical tools able to unravel their structure-activity relationships, and to alter their cellular levels. This last approach has been thoroughly studied by the development of specific inhibitors of some key enzymes that play an important role in biosynthesis or metabolism of these intriguing lipids. With the above premises in mind, the aim of this review is to collect, in a systematic way, the recent efforts described in the literature leading to the development of new chemical entities specifically designed to achieve the above goals.

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Section: Structural Modifications Of Sphingolipidsmentioning

confidence: 97%

Chemical Tools to Investigate Sphingolipid Metabolism and Functions

et al. 2007

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“…Moreover, it is unknown if concentrations of FTY720-P used in this study are found in human joints. In an animal study Matsumoto et al measured a mean serum concentration of 0.1 μM FTY720 after oral administration of 1 mg/kg to rats [27]. Assuming that similar concentrations are present in synovial fluid, the concentrations of FTY720-P used in the current study would exceed FTY720 levels in rats ten-fold.…”

Section: Discussionmentioning

confidence: 92%

The Immunosuppressant FTY720 (Fingolimod) enhances Glycosaminoglycan depletion in articular cartilage

Stradner

Angerer

Ortner

et al. 2011

BMC Musculoskelet Disord

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BackgroundFTY720 (Fingolimod) is a novel immunosuppressive drug investigated in clinical trials for organ transplantation and multiple sclerosis. It acts as a functional sphingosine-1-phosphate (S1P) receptor antagonist, thereby inhibiting the egress of lymphocytes from secondary lymphoid organs. As S1P is able to prevent IL-1beta induced cartilage degradation, we examined the direct impact of FTY720 on cytokine induced cartilage destruction.MethodsBovine chondrocytes were treated with the bioactive phosphorylated form of FTY720 (FTY720-P) in combination with IL-1beta or TNF-alpha. Expression of MMP-1,-3.-13, iNOS and ADAMTS-4,-5 and COX-2 was evaluated using quantitative real-time PCR and western blot. Glycosaminoglycan depletion from cartilage explants was determined using a 1,9-dimethylene blue assay and safranin O staining.ResultsFTY720-P significantly reduced IL-1beta and TNF-alpha induced expression of iNOS. In contrast FTY720-P increased MMP-3 and ADAMTS-5 mRNA expression. Furthermore depletion of glycosaminoglycan from cartilage explants by IL-1beta and TNF-alpha was significantly enhanced by FTY720-P in an MMP-3 dependent manner.ConclusionsOur results suggest that FTY720 may enhance cartilage degradation in pro-inflammatory environment.

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“…Both Matsumoto and co-workers (2006) 50 and Fujita and co-workers (2000) 51 wanted to establish a cost effective assay to determine the presence of FTY720 in blood samples after clinical trials. This led to the development of an immunoassay methodology.…”

Section: Development Of Antibodymentioning

confidence: 99%

“…Towards this, a variety of thiolbased analogues, which can readily undergo a Michael addi-tion reaction, were synthesized and studied. Amongst them two analogues, 2-amino-2-{2-[4-(8-mercaptooctyl)phenyl]ethyl}propane-1,3-diol hydrochloride (95a) 50 and a truncated version 2-amino-2-{2-[4-(4-mercaptobutyl)phenyl]ethyl}propane-1,3-diol hydrochloride (95b) 51 served as haptens (Scheme 21).…”

Section: Development Of Antibodymentioning

confidence: 99%

Perspective on FTY720, an Immunosuppressant

2018

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FTY720 {fingolimod hydrochloride, 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol hydrochloride}, a novel immunosuppressant, was discovered by chemical modification based on the structure activity relationships of ISP-I (myriocin), a metabolite of the fungus Isaria sinclairii. This short perspective provides insights to the various strategies available in the literature for the synthesis of FTY720 and its analogues.1 Introduction2 Classification of Immunosuppressive Drugs3 The Rise of FTY7204 Different Synthetic Strategies for FTY7205 Analogues of FTY7206 Binding Studies of FTY7207 Mode of Action8 Conclusion

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Preparation of antibodies against a novel immunosuppressant, FTY720, and development of an enzyme immunoassay for FTY720

Cited by 6 publications

References 28 publications

Chemical Tools to Investigate Sphingolipid Metabolism and Functions

Chemical Tools to Investigate Sphingolipid Metabolism and Functions

The Immunosuppressant FTY720 (Fingolimod) enhances Glycosaminoglycan depletion in articular cartilage

Perspective on FTY720, an Immunosuppressant

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