Fingolimod-d4 Clorhidrato
Descripción general
Descripción
Fingolimod-D4 Hydrochloride is a labelled analogue of Fingolimod. Fingolimod is an immunosuppressive agent used for the treatment of relapsing multiple sclerosis. It is a sphingosine-1-phosphate receptor modulator preventing lymphocyte emigration to participate in the autoimmune reaction.
Aplicaciones Científicas De Investigación
Cuantificación en Plasma Humano
Fingolimod-d4 Clorhidrato se utiliza en el desarrollo de métodos analíticos para cuantificar Fingolimod y su metabolito Fingolimod-Fosfato en plasma humano {svg_1}. Esto es particularmente útil para evaluar las diferencias interindividuales en la biodisponibilidad de estos compuestos y relacionar estas diferencias con la variabilidad en las respuestas clínicas {svg_2}.
Método UPLC Indicador de Estabilidad
this compound se utiliza en el desarrollo de un método UPLC indicador de estabilidad para la determinación cuantitativa de Fingolimod Clorhidrato y sus sustancias relacionadas {svg_3}. Este método es útil en el análisis de ingredientes farmacéuticos activos y formas de dosificación farmacéutica {svg_4}.
Tratamiento de la Esclerosis Múltiple
this compound se utiliza en el tratamiento de la esclerosis múltiple remitente-recurrente {svg_5}. Es un modulador del receptor de esfingosina 1-fosfato que puede reducir el número de recaídas en pacientes con esta forma de esclerosis múltiple {svg_6}.
Actividad Anticancerígena
this compound ha mostrado una posible actividad anticancerígena {svg_7}. Activa la proteína fosfatasa 2A, lo que genera efectos anticancerígenos {svg_8}. Se está explorando el desarrollo de análogos de Fingolimod que no se pueden fosforilar para mejorar su actividad anticancerígena {svg_9}.
Tratamiento de la Psicosis
this compound se ha utilizado en el tratamiento del comportamiento relacionado con la psicosis {svg_10}. Se ha demostrado que alivia la hipersensibilidad a la metanfetamina y mejora las medidas de neuroinflamación, como la activación microglial, la producción de citoquinas y la infiltración de leucocitos {svg_11}.
Promoción de la Angiogénesis
this compound se ha utilizado para promover la angiogénesis {svg_12}. Se ha demostrado que maximiza la osteoinductividad y mejora la incorporación de aloinjertos al reclutar células progenitoras óseas de los tejidos blandos circundantes y la microcirculación {svg_13}.
Mecanismo De Acción
Target of Action
Fingolimod-d4 Hydrochloride, also known as FTY720-d4 Hydrochloride, primarily targets the sphingosine 1-phosphate receptors (S1PRs) found on lymphocytes and other organs . The modulation of these receptors is crucial in managing multiple sclerosis (MS) symptoms .
Mode of Action
Fingolimod-d4 Hydrochloride acts as a sphingosine 1-phosphate receptor modulator . It is metabolized to its active form, fingolimod-phosphate, which binds to sphingosine 1-phosphate receptors 1, 3, 4, and 5 .
Biochemical Pathways
Fingolimod-d4 Hydrochloride affects several biochemical pathways. It induces metabolic reprogramming in brain regions, upregulating oxidative phosphorylation while downregulating glycolysis and the pentose phosphate pathway . It also modulates neuroinflammation by upregulating retrograde endocannabinoid signaling and autophagy pathways, and downregulating neuroinflammation-related pathways including neutrophil degranulation and the IL-12 mediated signaling pathway .
Pharmacokinetics
It’s known that the compound is given orally . More research is needed to fully understand the ADME properties of Fingolimod-d4 Hydrochloride and their impact on bioavailability.
Result of Action
The molecular and cellular effects of Fingolimod-d4 Hydrochloride’s action are profound. It reduces the number of lymphocytes in the peripheral blood, which is believed to be effective in treating MS due to the reduced lymphocytes into the CNS . It also induces numerous biological effects, including endothelial cell-cell adhesion, angiogenesis, vascular integrity, and cardiovascular function .
Action Environment
The action environment of Fingolimod-d4 Hydrochloride is primarily within the immune system and the CNS . The interaction with s1p receptors in various tissues accounts for the reported adverse effects
Análisis Bioquímico
Biochemical Properties
Fingolimod-d4 Hydrochloride interacts with sphingosine 1-phosphate receptors (S1PRs) to bring about an array of pharmacological effects . It exerts inhibitory effects on sphingolipid pathway enzymes, inhibits histone deacetylases, transient receptor potential cation channel subfamily M member 7 (TRMP7), cytosolic phospholipase A2α (cPLA2α), reduces lysophosphatidic acid (LPA) plasma levels, and activates protein phosphatase 2A (PP2A) .
Cellular Effects
Fingolimod-d4 Hydrochloride has profound effects on various types of cells and cellular processes. It can profoundly reduce T-cell numbers in circulation and the CNS, thereby suppressing inflammation and MS . It also induces apoptosis, autophagy, cell cycle arrest, epigenetic regulations, macrophages M1/M2 shift and enhances BDNF expression .
Molecular Mechanism
Fingolimod-d4 Hydrochloride exerts its effects at the molecular level through several mechanisms. It binds to S1P receptor4 (S1PR4) that is primarily expressed in lymphocytes and hematopoietic tissues . It can induce apoptotic pathways by activation of caspase cascades, enhancing PTEN which inhibits pAkt, and inducing (ROS-JNK-p53) loop-dependent autophagy .
Temporal Effects in Laboratory Settings
It has been shown that the drug has a significant therapeutic effect in immunodeficient mice, not in immunocompetent mice .
Dosage Effects in Animal Models
In an animal model of genetic absence epilepsy, Fingolimod (1 mg/kg) showed transient antiepileptic effects and longer-lasting anti-cognition decline . During the chronic epileptic phase of the mouse kainate model, 6 mg/kg of the drug also showed neuroprotective and anti-gliotic effects besides reducing seizure frequency .
Metabolic Pathways
Fingolimod-d4 Hydrochloride is involved in the sphingosine 1-phosphate (S1P) pathway . It is phosphorylated to Fingolimod-phosphate by two protein kinases, type-1 and type-2 sphingosine kinase (SphK1 and -2), enabling it to interact with sphingosine receptors .
Transport and Distribution
It is known that Fingolimod binds to S1P receptor4 (S1PR4) that is primarily expressed in lymphocytes and hematopoietic tissues .
Subcellular Localization
It is known that Fingolimod activates PP2A that plays a principal role as a regulator of cell cycle/division and growth .
Propiedades
IUPAC Name |
2-amino-1,1,3,3-tetradeuterio-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol;hydrochloride |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C19H33NO2.ClH/c1-2-3-4-5-6-7-8-17-9-11-18(12-10-17)13-14-19(20,15-21)16-22;/h9-12,21-22H,2-8,13-16,20H2,1H3;1H/i15D2,16D2; |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
SWZTYAVBMYWFGS-JWIOGAFXSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CCCCCCCCC1=CC=C(C=C1)CCC(CO)(CO)N.Cl |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Isomeric SMILES |
[2H]C([2H])(C(CCC1=CC=C(C=C1)CCCCCCCC)(C([2H])([2H])O)N)O.Cl |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C19H34ClNO2 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Weight |
348.0 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Synthesis routes and methods I
Procedure details
Synthesis routes and methods II
Procedure details
Retrosynthesis Analysis
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Strategy Settings
| Precursor scoring | Relevance Heuristic |
|---|---|
| Min. plausibility | 0.01 |
| Model | Template_relevance |
| Template Set | Pistachio/Bkms_metabolic/Pistachio_ringbreaker/Reaxys/Reaxys_biocatalysis |
| Top-N result to add to graph | 6 |
Feasible Synthetic Routes
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Tenga en cuenta que todos los artículos e información de productos presentados en BenchChem están destinados únicamente con fines informativos. Los productos disponibles para la compra en BenchChem están diseñados específicamente para estudios in vitro, que se realizan fuera de organismos vivos. Los estudios in vitro, derivados del término latino "in vidrio", involucran experimentos realizados en entornos de laboratorio controlados utilizando células o tejidos. Es importante tener en cuenta que estos productos no se clasifican como medicamentos y no han recibido la aprobación de la FDA para la prevención, tratamiento o cura de ninguna condición médica, dolencia o enfermedad. Debemos enfatizar que cualquier forma de introducción corporal de estos productos en humanos o animales está estrictamente prohibida por ley. Es esencial adherirse a estas pautas para garantizar el cumplimiento de los estándares legales y éticos en la investigación y experimentación.
![(2E,4R)-4-[(1R,3aS,4E,7aR)-4-[(2E)-2-[(3S,5R)-3,5-Bis[[(tert-butyl)dimethylsilyl]oxy]-2-methylenecyclohexylidene]ethylidene]octahydro-7a-methyl-1H-inden-1-yl]-1-cyclopropyl-2-penten-1-one](/img/structure/B602404.png)
