Fingolimod hydrochloride

Modify Date: 2024-01-02 17:51:22

Fingolimod hydrochloride structure	Common Name	Fingolimod hydrochloride
	CAS Number	162359-56-0	Molecular Weight	343.932
	Density	1.016g/cm3	Boiling Point	479.5ºC at 760 mmHg
	Molecular Formula	C₁₉H₃₄ClNO₂	Melting Point	102-107ºC
	MSDS	Chinese USA	Flash Point	243.8ºC
	Symbol	GHS07	Signal Word	Warning

Use of Fingolimod hydrochloride

Fingolimod hydrochloride is a sphingosine 1-phosphate (S1P) antagonist with an IC50 of 0.033 nM in K562 and NK cells.

Name	fingolimod hydrochloride
Synonym	More Synonyms

Description	Fingolimod hydrochloride is a sphingosine 1-phosphate (S1P) antagonist with an IC50 of 0.033 nM in K562 and NK cells.
Related Catalog	Signaling Pathways >> GPCR/G Protein >> LPL Receptor Research Areas >> Inflammation/Immunology
Target	IC50: 0.033 nM (S1P, in K562 and NK cells)[1]
In Vitro	The monocyte-derived immature dendritic cells (iDCs) are pretreated with various concentrations of S1P for various periods of time prior to their incubation with NK cells. Four hours incubation of autologous or allogeneic iDCs with 0.2-20 μM of S1P significantly protectes these cells from NK cell lysis. The IC50 values of S1P are calculated at 160 nM for autologous iDCs, and 34 nM for allogeneic iDCs. Next, the inhibitory effect of S1P is revered by various concentrations of Fingolimod hydrochloride (FTY720) or SEW2871, with an IC50 effect of 173 or 15 nM, respectively[1]. The immunomodulator Fingolimod hydrochloride (FTY720) is a structural analogue of S1P and acts in its phosphorylated isoform as an unselective agonist on S1P1 and S1P3-5 and a selective functional antagonist on S1P1. FTY720 enhances serum S1P levels by inhibiting S1P lyase activity[2]. The number of Iba1+ cells in ipsilateral CA3 is counted, and the corresponding graph shows a significantly lower number of Iba1+ cells in CA3 of the Kainic acid (KA)+FTY720 group than in CA3 of KA group[3].
In Vivo	Administration of the immunomodulator Fingolimod hydrochloride (0.1 mg/kg i.v.) increases serum S1P, improves impaired systolic contractility and activates the PI3K-pathway in the heart. Administration of Fingolimod hydrochloride (FTY720) causes a significant rise in serum S1P levels in both sham-operated animals and animals challenged with LPS/PepG (P<0.0001)[2]. FTY720 attenuates microgliosis, modulates the microglia inflammatory phenotype by reducing LPS-mediated activation of p38 MAPK signalling pathway. Thus, FTY720 shares both direct neuroprotective and anti-inflammatory properties that can contribute to overall neuroprotection. In particular, the potential of FTY720 to switch microglia phenotype from a detrimental to a protective one represents a therapeutic mechanism for attenuating acute and chronic CNS damage[3].
Cell Assay	Immature dendritic cells (DCs) are left intact or are incubated with 2 μM S1P, 10 nM Fingolimod hydrochloride, 10 nM SEW2871 or the combinations of S1P with these drugs for 4 h. As a control 1 μg/mL LPS is used. The cells are washed and incubated in a 96-well plate (v-bottom, 2×105 cells per well), washed again and resuspended in PBS buffer containing 0.1% sodium azide. They are labeled with 1 μg/mL FITC-conjugated mouse anti-human CD80, 1 μg/mL FITC-conjugated mouse anti-human CD83, 1 μg/mL FITC-conjugated mouse anti-human CD86, 1 μg/mL FITC-conjugated mouse anti-human HLA-class I, 1 μg/mL FITC-conjugated mouse anti-human HLA-DR, 1 μg/mL FITC-conjugated mouse anti-human HLA-E, or 1 μg/mL FITC-conjugated mouse IgG as a control. The cells are washed twice, and examined in the flow cytometer. Markers are set according to the isotype control FITC-conjugated mouse IgG[1].
Animal Admin	Mice[2] This study is carried out on 2-month-old male C57BL/6J mice or sphingosine kinase-2 deficient (SPHK-2-/-) mice weighing 25-30 g, receiving a standard diet and water ad libitum. C57BL/6J wild-type or SPHK-2-/- mice receives i.p.-injections of LPS (9 mg/kg)/PepG (1 mg/kg) or its vehicle (0.9% saline). Sham mice are not subjected to LPS/PepG, but are otherwise treated in the same way. At 1 h after LPS/PepG challenge, mice are treated with Fingolimod hydrochloride (0.1 mg/kg i.v.) or its vehicle (10% DMSO). To elucidate the role of different S1P receptors in the observed effects of Fingolimod hydrochloride, mice receive (45 min after LPS/PepG and 15 min prior to Fingolimod hydrochloride) the selective PI3K inhibitor LY294002 (0.3 mg/kg i.v.) or the selective S1P2 receptor antagonist JTE 013 (1 mg/kg i.v.) or (1 h after LPS/PepG) the selective S1P1 receptor agonist SEW2871 (1 mg/kg i.v.) or vehicle (10% DMSO). Rat[3] The Sprague-Dawley rats (200 to 250 g) are used. Fingolimod hydrochloride is applied icv (1 μg/2 μL), together with Kainic acid (KA), plus intraperitoneally (ip; 1 mg/kg) 24 h before, and daily, until sacrifice 3 days aftericv. Rats are evaluated for neurological score, neuronal loss in CA3 hippocampal region and activation of microglia at the lesion site.
References	[1]. Rolin J, et al. FTY720 and SEW2871 reverse the inhibitory effect of S1P on natural killer cell mediated lysis of K562 tumor cells and dendritic cells but not on cytokine release. Cancer Immunol Immunother. 2010, 59(4), 575-586. [2]. Coldewey SM, et al. Elevation of serum sphingosine-1-phosphate attenuates impaired cardiac function in experimental sepsis. Sci Rep. 2016 Jun 9;6:27594. [3]. Cipriani R, et al. FTY720 attenuates excitotoxicity and neuroinflammation. J Neuroinflammation. 2015 May 8;12:86.

Density	1.016g/cm3
Boiling Point	479.5ºC at 760 mmHg
Melting Point	102-107ºC
Molecular Formula	C₁₉H₃₄ClNO₂
Molecular Weight	343.932
Flash Point	243.8ºC
Exact Mass	343.227814
PSA	66.48000
LogP	4.70660
Vapour Pressure	5.28E-10mmHg at 25°C
Index of Refraction	1.531
Storage condition	-20°C Freezer

Fingolimod hydrochloride MSDS(Chinese)

Symbol	GHS07
Signal Word	Warning
Hazard Statements	H315-H319-H335-H412
Precautionary Statements	P261-P273-P305 + P351 + P338
Hazard Codes	Xi
Risk Phrases	36/37/38-52/53
Safety Phrases	26-61
RIDADR	NONH for all modes of transport
HS Code	2922199090

HS Code	2922199090
Summary	2922199090. other amino-alcohols, other than those containing more than one kind of oxygen function, their ethers and esters; salts thereof. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

Fingolimod and risk of varicella-zoster virus infection: back to the future with an old infection and a new drug.

JAMA Neurol. 72(1) , 10-3, (2015)

Varicella-zoster virus infections in patients treated with fingolimod: risk assessment and consensus recommendations for management.

JAMA Neurol. 72(1) , 31-9, (2015)

Varicella-zoster virus (VZV) infections increasingly are reported in patients with multiple sclerosis (MS) and constitute an area of significant concern, especially with the advent of more disease-mod...

Initial lymphocyte count and low BMI may affect fingolimod-induced lymphopenia.

Neurology 83(23) , 2153-7, (2014)

To assess whether pretreatment-lymphocyte counts, treatment before fingolimod, age, sex, or body mass index (BMI) affects the risk of fingolimod-induced lymphopenia in patients with relapsing-remittin...

FTY720 Hydrochloride

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FTY720

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2-Amino-2-[2-(4-n-octylphenyl)ethyl]propane-1,3-diol Hydrochloride

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1,3-Propanediol, 2-amino-2-[2-(4-octylphenyl)ethyl]-, hydrochloride (1:1)

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2-Amino-2-[2-(4-octylphényl)éthyl]-1,3-propanediol chlorhydrate

2-Amino-2-[2-(4-octyl-phenyl)-ethyl]-propane-1,3-diol hydrochloride Fingolimod hydrochloride

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MFCD00939512

Fingolimod (hydrochloride)

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