SPL-410
目录号 : GC37675
SPL-410 是具有口服活性的、强效的、选择性的、羟乙胺类的类信号肽肽酶 2a (SPPL2a) 的抑制剂，其IC50 值为 9 nM。
Cas No.:2351886-00-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
SPL-410 is an orally active, highly potent and selective hydroxyethylamine based SPPL2a (Signal Peptide Peptidase Like 2a) inhibitor, with an IC50 of 9 nM[1]. IC50: 9 nM (SPPL2a)[1].
[1]. Velcicky J, et al. Discovery of Orally Active Hydroxyethylamine Based SPPL2a Inhibitors. ACS Med Chem Lett. 2019 May 23;10(6):887-892.
| Cas No. | 2351886-00-3 | SDF | |
| Canonical SMILES | N[C@H]([C@@H](O)CN(C1CCC1)S(C2=CC=C(C(C)(C)C)C=C2)(=O)=O)C3=CC=C(OC(F)(F)F)C=C3 | ||
| 分子式 | C24H31F3N2O4S | 分子量 | 500.57 |
| 溶解度 | DMSO : 190 mg/mL (379.57 mM; Need ultrasonic) | 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 | 1.9977 mL | 9.9886 mL | 19.9772 mL |
| 5 mM | 0.3995 mL | 1.9977 mL | 3.9954 mL |
| 10 mM | 0.1998 mL | 0.9989 mL | 1.9977 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。
Discovery of Orally Active Hydroxyethylamine Based SPPL2a Inhibitors
ACS Med Chem Lett 2019 May 23;10(6):887-892.PMID:31223443DOI:PMC6580379
SPPL2a (Signal Peptide Peptidase Like 2a) is an intramembrane aspartyl protease engaged in the function of B-cells and dendritic cells. Despite being an attractive target for modulation of the immune system, selective SPPL2a inhibitors are barely described in the literature. Recently, we have disclosed a selective, small molecular weight agent SPL-707 which confirmed that pharmacological inhibition of SPPL2a leads to the accumulation of its substrate CD74/p8 and as a consequence to a reduction in the number of B-cells as well as myeloid dendritic cells in mice. In this paper we describe the discovery of novel hydroxyethylamine based SPPL2a inhibitors. Starting from a rather lipophilic screening hit, several iterative optimization cycles allowed for its transformation into a highly potent and selective compound 15 (SPL-410) which inhibited in vivo CD74/p8 fragment processing in mice at 10 mg/kg oral dose.