| Size | Price | |
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| 500mg | ||
| 1g | ||
| Other Sizes |
Purity: ≥98%
Amiselimod, formerly known as MT1303, is a potent and selective immunosuppressant and sphingosine 1 phosphate receptor modulator. Amiselimod may be potentially useful for treatment of multiple sclerosis; inflammatory diseases; autoimmune diseases; psoriasis and inflammatory bowel diseases. Amiselimod is currently being developed by Mitsubishi Tanabe Pharma Corporation.
Amiselimod (development code MT-1303) is a novel, potent, and selective oral sphingosine-1-phosphate receptor-1 (S1P₁ receptor) modulator belonging to the immunosuppressant class. The compound was developed by Mitsubishi Tanabe Pharma Corporation to improve the cardiac safety profile, particularly bradycardia, associated with first-generation S1P receptor modulators such as fingolimod. Amiselimod is phosphorylated in vivo to its active metabolite, Amiselimod-P, which acts as a functional antagonist of the S1P₁ receptor to regulate lymphocyte trafficking and exert immunomodulatory effects. The drug is primarily being developed for the treatment of autoimmune diseases, including inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis, and systemic lupus erythematosus (SLE).| Targets |
The primary target of Amiselimod is the sphingosine-1-phosphate receptor-1 (S1P₁ receptor). Its active metabolite, Amiselimod-P, exhibits extremely high affinity for this receptor, with an EC₅₀ value as low as 0.075 nM. As a functional antagonist, Amiselimod-P binds to the S1P₁ receptor and induces receptor internalization, leading to downregulation of S1P₁ receptor expression on the lymphocyte surface. This prevents lymphocyte egress from lymph nodes and reduces the infiltration of autoreactive T cells into sites of inflammation. In terms of receptor selectivity, Amiselimod-P also exhibits agonistic activity at the S1P₅ receptor (EC₅₀ = 0.47 nM), weak agonistic activity at the S1P₄ receptor (EC₅₀ = 122.3 nM), and no distinct agonistic activity at the S1P₂ or S1P₃ receptors (EC₅₀ > 10,000 nM). Additionally, Amiselimod-P activates G-protein-activated inwardly rectifying potassium (GIRK) channels with an EC₅₀ of 41.6 nM.
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| ln Vitro |
In vitro, Amiselimod exerts its biological effects primarily through its active metabolite, Amiselimod-P. In calcium mobilization assays, Amiselimod-P exhibits potent and selective agonistic activity at the human S1P₁ receptor, with an EC₅₀ of 0.075 nM. It shows EC₅₀ values of 0.47 nM at the S1P₅ receptor and 122.3 nM at the S1P₄ receptor, with no significant activity at S1P₂ or S1P₃ receptors (EC₅₀ > 10,000 nM). In acutely isolated human atrial myocytes, Amiselimod-P activates GIRK currents in a concentration-dependent manner with an EC₅₀ of 41.6 nM, which is approximately 5-fold weaker than fingolimod-P (EC₅₀ = 8.5 nM) and 20-fold weaker than S1P (EC₅₀ = 1.9 nM). In vitro phosphorylation studies in HEK293 cells and primary human cardiac myocytes (HCMs) showed that the conversion of Amiselimod to its active phosphate metabolite (Amiselimod-P) is slower than the conversion of fingolimod to fingolimod-P. Amiselimod-P was first detected after 6 hours of incubation, and its concentration after 12 hours was about half that of fingolimod-P generated under the same conditions.
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| ln Vivo |
Amiselimod demonstrates significant in vivo efficacy in various animal models of autoimmune diseases. In a CD4+CD45RBhigh T cell adoptive transfer-induced chronic colitis model of IBD, once-daily oral administration of Amiselimod at 0.1 mg/kg and 0.3 mg/kg significantly inhibited the development of chronic colitis, with efficacy comparable to that of an anti-mouse TNF-α monoclonal antibody (250 μg/mouse). Amiselimod treatment significantly reduced the number of infiltrating Th1 and Th17 cells in the colonic lamina propria. In two murine systemic lupus erythematosus (SLE) models, MRL/lpr and NZBWF1 mice, once-daily oral administration of 0.1 and 0.3 mg/kg Amiselimod not only inhibited the development of lupus nephritis (prophylactic administration) but also improved established lupus nephritis symptoms (therapeutic administration), with efficacy superior or comparable to that of FK506 (1 and 3 mg/kg). Histological analysis showed that Amiselimod treatment inhibited T cell infiltration into the kidneys, mesangial expansion, and glomerulosclerosis. In normal mice, oral administration of Amiselimod (0.3 mg/kg once daily for 3 days) almost completely abolished S1P₁ receptor expression on CD4+ T cells from mesenteric lymph nodes and significantly decreased CD4+ T cell counts in peripheral blood.
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| Enzyme Assay |
The receptor binding and functional activity of Amiselimod-P are typically assessed using cell-based functional assays rather than traditional cell-free enzymatic assays. A representative method is the calcium mobilization assay: CHO cells stably expressing human S1P₁, S1P₂, S1P₃, S1P₄, or S1P₅ receptors are seeded in 96-well plates, loaded with a calcium-sensitive dye (such as Fluo-4 AM), and incubated at 37°C. Increasing concentrations of Amiselimod-P (0.001 nM–10 μM) are added, and fluorescence signals resulting from changes in intracellular calcium concentration are measured using a fluorescence plate reader. S1P is used as a positive control, and EC₅₀ values are calculated by nonlinear regression fitting. For cell-free receptor binding assays, a radioligand competitive binding method can be used: membrane preparations from cells expressing specific S1P receptors are incubated with a fixed concentration of radiolabeled S1P (such as ³³P-S1P) and increasing concentrations of unlabeled Amiselimod-P. Membrane-bound fractions are collected by filtration, and radioactivity is measured using a scintillation counter to calculate IC₅₀ values. Specific binding affinity values for Amiselimod at the S1P₁ receptor are not provided in the search results, but the functional EC₅₀ is reported as 0.075 nM.
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| Cell Assay |
In vitro cellular activity assessment of Amiselimod primarily employs the following types of assays. First, phosphorylation assays: Human embryonic kidney 293 (HEK293) cells or primary human cardiac myocytes (HCMs) are incubated with Amiselimod (1 μM) for 0-24 hours, lysed, and the concentration of generated Amiselimod-P is measured by LC-MS/MS to evaluate phosphorylation efficiency in different cell types. Second, GIRK channel activation assays: Human atrial myocytes are acutely isolated from atrial tissue, and GIRK currents are recorded using the whole-cell patch-clamp technique. Cells are voltage-clamped at -50 mV, increasing concentrations of Amiselimod-P (0.1 nM–10 μM) are applied, and EC₅₀ values are calculated from changes in current amplitude. Third, lymphocyte S1P₁ receptor expression detection: CD4+ T cells are isolated from mice (after in vivo administration of Amiselimod at 0.3 mg/kg) or incubated directly with Amiselimod-P in vitro, and S1P₁ receptor expression levels on the cell surface are detected by flow cytometry.
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| Animal Protocol |
The in vivo efficacy of Amiselimod is evaluated using various autoimmune disease animal models. Using the chronic colitis IBD model as an example: CD4+CD45RBhigh T cells (purity >95%) are isolated from BALB/c mice and injected via the tail vein (3 × 10⁵ cells/mouse) into SCID mice to induce chronic colitis. Starting from day 7 after cell transfer, Amiselimod is orally administered daily at doses of 0.03, 0.1, or 0.3 mg/kg for 21 consecutive days. The positive control group receives intraperitoneal injections of anti-mouse TNF-α monoclonal antibody (250 μg/mouse) on days 7 and 21. Body weight is monitored weekly, and clinical scores (including body weight loss, diarrhea, and fecal blood) are assessed on day 28. After euthanasia, colon tissues are collected for H&E staining and histological scoring, and immune cell infiltration (Th1, Th17, etc.) in the lamina propria is analyzed by flow cytometry. In SLE models, MRL/lpr or NZBWF1 mice receive daily oral administration of Amiselimod at 0.1 or 0.3 mg/kg for 8-13 weeks, with monitoring of proteinuria and serum anti-dsDNA antibody levels. After euthanasia, kidneys are collected for H&E and PAS staining to evaluate glomerulosclerosis, mesangial expansion, and T cell infiltration. Pharmacodynamic studies also include peripheral blood lymphocyte subset counts via orbital bleeding, and quantification of T cells, B cells, and plasma cells in lymph nodes and spleen by flow cytometry.
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| ADME/Pharmacokinetics |
The pharmacokinetic profile of Amiselimod in humans was determined through a radiolabeled mass balance study. Following a single oral dose of 0.4 mg [¹⁴C]-Amiselimod in healthy male subjects, plasma drug concentrations reached a maximum at 12 hours post-dose (Tmax = 12 h), followed by a slow decline with an extremely long half-life (t₁/₂ = 451 hours, approximately 18.8 days). By the final assessment on Day 57, the total recovery of administered radioactivity was 91.16%, with 35.32% excreted in urine and 55.84% in feces. The most abundant metabolite in plasma was the active metabolite Amiselimod-P, accounting for 42.6% of the total radioactivity AUC. The major excretory component in urine was the HU4 metabolite, accounting for 28.1% of sample radioactivity (4.05% of the dose); the major component in feces was parent Amiselimod, accounting for 89.8% of sample radioactivity (25.49% of the dose) up to 240 hours post-administration. The study indicates that multiple metabolic pathways are involved in the elimination of Amiselimod from the human body, and renal excretion of Amiselimod and its active metabolite Amiselimod-P is low. Therefore, Amiselimod is unlikely to cause conspicuous drug interactions, and its pharmacokinetics in patients with renal impairment are not expected to be significantly affected.
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| Toxicity/Toxicokinetics |
The safety profile of Amiselimod is primarily characterized by its improved cardiac toxicology profile. Compared to the first-generation S1P receptor modulator fingolimod, Amiselimod demonstrates a better cardiac safety profile in both preclinical and clinical studies. In GIRK current activation assays in isolated human atrial myocytes, Amiselimod-P activates GIRK currents with an EC₅₀ of 41.6 nM, which is approximately 5-fold weaker than fingolimod-P (EC₅₀ = 8.5 nM), suggesting that at equivalent S1P₁ receptor modulating doses, the risk of bradycardia associated with Amiselimod is significantly reduced. Furthermore, the slower phosphorylation rate of Amiselimod in HEK293 cells and human cardiac myocytes compared to fingolimod also contributes to reduced cardiac exposure and side effect risks. In animal models, Amiselimod is well tolerated at doses of 0.1-0.3 mg/kg. The Material Safety Data Sheet (MSDS) for Amiselimod hydrochloride classifies it as a non-hazardous substance, with no carcinogenicity findings (not listed by NTP, IARC, OSHA, or ACGIH), although it notes that irritating fumes may be released upon combustion. The toxicological effects of this compound have not been thoroughly studied, and it is limited to research use only, not for human diagnostic or therapeutic purposes.
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| References |
[1]. Amiselimod (MT-1303), a novel sphingosine 1-phosphate receptor-1 functional antagonist, inhibits progress of chronic colitis induced by transfer of CD4+CD45RBhigh T cells. PLoS One. 2019 Dec 5;14(12):e0226154.
[2]. Amiselimod, a novel sphingosine 1-phosphate receptor-1 modulator, has potent therapeutic efficacy for autoimmune diseases, with low bradycardia risk. Br J Pharmacol. 2017 Jan;174(1):15-27. |
| Molecular Formula |
C19H30F3NO3
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|---|---|
| Molecular Weight |
377.45
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| Exact Mass |
377.217
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| Elemental Analysis |
C, 60.46; H, 8.01; F, 15.10; N, 3.71; O, 12.72
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| CAS # |
942399-20-4
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| Related CAS # |
942399-20-4;942398-84-7 (HCl);
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| PubChem CID |
16129483
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
535.1±50.0 °C at 760 mmHg
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| Flash Point |
277.4±30.1 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.497
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| LogP |
5.21
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
26
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| Complexity |
376
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(C1=C(C([H])=C([H])C(=C1[H])C([H])([H])C([H])([H])C(C([H])([H])O[H])(C([H])([H])O[H])N([H])[H])OC([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])(F)F
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| InChi Key |
2-Amino-2-{2-[4-(heptyloxy)-3-(trifluoromethyl)phenyl]ethyl}propane-1,3-diol
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| InChi Code |
JVCPIJKPAKAIIP-UHFFFAOYSA-N
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| Chemical Name |
Amiselimod MT1303 MT-1303 MT 1303 Amiselimod free base
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| Synonyms |
Amiselimod; 942399-20-4; MT-1303 FREE BASE; MT1303; MT 1303; 358M5150LY; DTXSID301141402;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6494 mL | 13.2468 mL | 26.4936 mL | |
| 5 mM | 0.5299 mL | 2.6494 mL | 5.2987 mL | |
| 10 mM | 0.2649 mL | 1.3247 mL | 2.6494 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02193217 | Completed | Drug: MT-1303-Low Drug: MT-1303-High |
Relapsing-remitting Multiple Sclerosis |
Mitsubishi Tanabe Pharma Corporation |
N/A | Phase 1 |
Products are for research use only; We do not sell to patients
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