| 名称 | Ponesimod |
| 描述 | Ponesimod (ACT-128800) is an orally available sphingosine-1-phosphate receptor 1 (S1PR1, S1P1) agonist with potential immunomodulating activity. |
| 激酶实验 | The enzymatic reactions are conducted in duplicate at room temperature for 1 hour in a 50 μL mixture containing PKMT assay buffer, substrate coated plate, 10 M SAM, a HMT enzyme (EZH2 (800 ng/reaction), MLL (300 ng/reaction), PRMT1 (0.5 ng/reaction), SUV39H1 (75 ng/reaction) and UNC0638 (0-1.25 μM). After enzymatic reactions, 100 μL of first antibody is added to each well and the plate is incubated at room temperature for an additional 1 h. 100 μL of secondary antibody is added to each well and the plate is incubated at room temperature for an additional 30 min. 100 μL of developer reagents are added to wells and luminescence is measured using a BioTek SynergyTM 2 microplate reader. Enzyme activity assays are performed in duplicates at each concentration. The luminescence data are analyzed using the computer software, Graphpad Prism[1]. |
| 体外活性 | Relative to the potency of S1P, the potency of ponesimod at human recombinant receptors was 4.4-fold higher for S1P1 and 150-fold lower for human S1P3. Therefore, ponesimod was ～650-fold more selective for human S1P1 over S1P3 than the natural ligand[1]. |
| 体内活性 | Ponesimod is a new, potent, and selective S1P1 receptor agonist with pharmacokinetic properties allowing rapid restoration of lymphocyte count in peripheral blood upon discontinuation. Ponesimod prevents edema formation, inflammatory cell accumulation, and cytokine release in the skin of mice with delayed-type hypersensitivity. Ponesimod also prevents the increase in paw volume and joint inflammation in rats with adjuvant-induced arthritis. Selective activation of S1P1 using ponesimod leads to blood lymphocyte count reduction and prevention in models of lymphocyte-mediated tissue inflammation. It has the potential to be as effective in animal models of autoimmunity and human autoimmune disease via its effect on T and B cell blood count. Thus, ponesimod may represent a new therapeutic option for the treatment of autoimmune diseases[1]. Ponesimod is eliminated within 1 week of discontinuation and its pharmacological effects are rapidly reversible [2]. |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 55 mg/mL (119.31 mM)
Ethanol : 92 mg/mL (199.58 mM)
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| 关键字 | S1P1 | Lysophospholipid Receptor | inflammation | LPL Receptor | Inhibitor | inhibit | ACT128800 | lymphocyte-mediated | ACT 128800 | Ponesimod |
| 相关产品 | Fingolimod hydrochloride | SLP9101555 | SKI-178 | LX-2931 | Tyloxapol | ASP-4058 | Ki16198 | Siponimod | Fingolimod | MP-A08 | S1PR1 modulator 1 | Ozanimod |
| 相关库 | 经典已知活性库 | 神经退行性疾病化合物库 | 膜蛋白靶向化合物库 | EMA 上市药物库 | 抗癌临床化合物库 | 药物功能重定位化合物库 | FDA 上市药物库 | 抗癌上市药物库 | 已知活性化合物库 | GPCR靶点分子库 |
United States
