AKP-11
目录号 : GC45681An S1P1 receptor agonist
Cas No.:1220973-37-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
AKP-11 is an agonist of sphingosine-1-phosphate receptor 1 (S1P1) with an EC50 value of 0.047 μM for [35S]GTPγS binding to CHO-K1 cell membranes expressing the human receptor.1 It decreases surface expression of S1P1 and increases phosphorylation of Akt and ERK in CHO cells expressing S1P1-HA when used at a concentration of 100 nM.2 AKP-11 (1.3 and 3 mg/kg) reduces protein levels of IFN-γ and IL-17 in spinal cord tissue and decreases disease severity in a rat model of experimental autoimmune encephalomyelitis (EAE). It decreases peripheral counts of total lymphocytes and total, CD4+, CD8+, and CD26L+ T cells in an EAE rat model, as well as in health control animals, when administered at a dose of 1.3 mg/kg.
|2. Samuvel, D.J., Saxena, N., Dhindsa, J.S., et al. AKP-11 - A novel S1P1 agonist with favorable safety profile attenuates experimental autoimmune encephalomyelitis in rat model of multiple sclerosis. PLoS One 10(10):e0141781, (2015).
| Cas No. | 1220973-37-4 | SDF | |
| Canonical SMILES | ClC1=C(OCCC)C=CC(C2=NC(C3=CC=C(OC(C(CO)(N)CO)=C4)C4=C3)=NO2)=C1 | ||
| 分子式 | C22H22ClN3O5 | 分子量 | 443.9 |
| 溶解度 | DMF: 5 mg/ml,DMSO: 20 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2528 mL | 11.2638 mL | 22.5276 mL |
| 5 mM | 0.4506 mL | 2.2528 mL | 4.5055 mL |
| 10 mM | 0.2253 mL | 1.1264 mL | 2.2528 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
AKP-11 - A Novel S1P1 Agonist with Favorable Safety Profile Attenuates Experimental Autoimmune Encephalomyelitis in Rat Model of Multiple Sclerosis
PLoS One 2015 Oct 29;10(10):e0141781.PMID:26513477DOI:PMC4626178
Sphingosine-1-phosphate receptor 1 (S1P1) mediated regulation of lymphocyte egress from lymphoid organs is recognized as the mechanism of FTY720 (Fingolimod, Gilenya) efficacy in relapsing-remitting forms of multiple sclerosis (RRMS). In this study we describe a novel S1P1 agonist AKP-11, next generation of S1P1 agonist, with immunomodulatory activities in cell culture model and for therapeutic efficacy against an animal model of MS, i.e. experimental autoimmune encephalomyelitis (EAE) but without the adverse effects observed with FTY720. Like FTY720, AKP-11 bound to S1P1 is internalized and activates intracellular AKT and ERKs cellular signaling pathways. In contrast to FTY720, AKP-11 mediated S1P1 downregulation is independent of sphingosine kinase activity indicating it to be a direct agonist of S1P1. The S1P1 loss and inhibition of lymphocyte egress by FTY720 leads to lymphopenia. In comparison with FTY720, oral administration of AKP-11 caused milder and reversible lymphopenia while providing a similar degree of therapeutic efficacy in the EAE animal model. Consistent with the observed reversible lymphopenia with AKP-11, the S1P1 recycled back to cell membrane in AKP-11 treated cells following its withdrawal, but not with withdrawal of FTY720. Accordingly, a smaller degree of ubiquitination and proteolysis of S1P1 was observed in AKP-11 treated cells as compared to FTY720. Consistent with previous observations, FTY720 treatment is associated with adverse effects of bradycardia and lung vascular leaks in rodents, whereas AKP-11 treatment had undetectable effects on bradycardia and reduced lung vascular leaks as compared to FTY720. Taken together, the data documents that AKP-11 treatment cause milder and reversible lymphopenia with milder adverse effects while maintaining therapeutic efficacy similar to that observed with FTY720, thus indicating therapeutic potential of AKP-11 for treatment of MS and related autoimmune disorders.