Repositioning Candidate Details
| Candidate ID: | R1446 |
| Source ID: | DB12371 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Siponimod |
| Synonyms: | Siponimod |
| Molecular Formula: | C29H35F3N2O3 |
| SMILES: | CCC1=CC(=CC=C1CN1CC(C1)C(O)=O)C(\C)=N\OCC1=CC=C(C2CCCCC2)C(=C1)C(F)(F)F |
| Structure: |
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| DrugBank Description: | Siponimod, also known as _Mayzent_, by Novartis, is a new drug formulated for the management of Multiple Sclerosis (MS). It was approved by the FDA on March 26, 2019 and by Health Canada on February 20, 2020. This drug is considered a _sphingosine-1-phosphate (S1P) receptor modulator_ and is thought to play a role in suppressing the central nervous system inflammation that is associated with MS . Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system that is chronic and inflammatory, disrupting communication between the brain and other parts of the body. Most patients diagnosed with this illness experience their initial disease symptoms between the age of 20 to 40, often the most productive years of life. Symptoms may include but are not limited to fatigue, gait changes, bowel or bladder dysfunction, abnormal muscle twitching, vision disturbance, and depressing or mood swings. MS is one of the most common causes of neurological disability in young adults and is found to occur more frequently in women than in men. |
| CAS Number: | 1230487-00-9 |
| Molecular Weight: | 516.605 |
| DrugBank Indication: | This drug is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults . |
| DrugBank Pharmacology: | **Immune system effects** Siponimod causes a dose-dependent decrease of the peripheral blood lymphocyte count within 6 hours of the first dose, caused by the reversible accumulation of lymphocytes in lymphoid tissues, due to lack of lymphocyte release . This results in a decrease in the inflammation that is involved in multiple sclerosis. Lymphocyte counts return to normal in 90% of patients within 10 days after the cessation of therapy . **Effects on heart rate and rhythm** Siponimod causes a temporary decrease in heart rate and atrioventricular conduction upon beginning treatment. The maximum fall in heart rate is observed in the first 6 hours post ingestion. Autonomic heart responses, including diurnal variation of heart rate and response to exercise activities, are not altered by siponimod treatment . **Effects on pulmonary function** Dose-dependent decreases in absolute forced expiratory volume over a time frame of 1 second were noted in siponimod-treated patients and were higher than in patients taking placebo . |
| DrugBank MoA: | Inflammation of the white and gray matter tissues in the central nervous system caused by localized immune cell infiltration and their cytokines are the initial cause of damage in MS. B lymphocytes and their cytokines are other factors in the pathogenesis of MS. Lymphotoxin and TNF-α produced by these cells encourage inflammation . The S1P receptor is an important receptor related to the function of lymphocytes and can be found in the central nervous system . S1P receptor (S1PR) signaling is associated with a wide variety of physiological processes for lymphocytes, including their egress and recirculation . Siponimod is classified as a sphingosine-1-phosphate (S1P) receptor modulator. Siponimod binds with high affinity to both S1P receptors 1 and 5. This drug blocks the ability of lymphocytes to release from the lymph nodes, decreasing the number of lymphocytes found in the peripheral blood. The mechanism by which siponimod exerts therapeutic effects in multiple sclerosis is not known at this time, but may involve the abovementioned decrease of lymphocytes into the central nervous system, decreasing the inflammatory effects of MS . |
| Targets: | Sphingosine 1-phosphate receptor 5 modulator; Sphingosine 1-phosphate receptor 1 |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
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