Seco Rapamycin
(Synonyms: 依维莫司杂质DCP,Secorapamycin A) 目录号 : GC37615
A degradation product of rapamycin
Cas No.:147438-27-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >85.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Rapamycin is a natural macrolide immunosuppressant that activates mTORC1. Seco rapamycin (sodium salt) is a nonenzyme-dependent degradation product of rapamycin resulting from ester hydration followed by dehydration.1 It has less than 4% of the potency of rapamycin in a thymocyte proliferation assay.1 Rapamycin quickly degrades to two ring-opened products, including seco rapamycin, in the cytoplasm or in homogenates of Caco-2 cells.2 Like rapamycin, seco rapamycin is secreted from cells by P-glycoprotein and metabolized to a common dihydro species.3 While seco rapamycin poorly activates mTOR, it mimics rapamycin in its ability to inhibit the proteasome.4
1.Wang, C.P., Chan, K.W., Schiksnis, R.A., et al.High performance liquid chromatographic isolation, spectroscopic characterization, and immunosuppressive activities of two rapamycin degradation productsJ. Liq. Chromatogr.17(16)3383-3392(1994) 2.Paine, M.F., Leung, L.Y., Lim, H.K., et al.Identification of a novel route of extraction of sirolimus in human small intestine: Roles of metabolism and secretionJ. Pharmacol. Exp. Ther.301(1)174-186(2002) 3.Paine, M.F., Leung, L.Y., and Watkins, P.B.New insights into drug absorption: Studies with sirolimusTher. Drug Monit.26(5)463-467(2004) 4.Osmulski, P.A., and Gaczynska, M.Rapamycin allosterically inhibits the proteasomeMol. Pharmacol.84(1)104-113(2013)
| Cas No. | 147438-27-5 | SDF | |
| 别名 | 依维莫司杂质DCP,Secorapamycin A | ||
| Canonical SMILES | O=C([C@H]1N(C(C([C@@]2(O)[C@H](C)CC[C@@H](C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C([C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(/C=C/[C@H](C)C[C@H]3C[C@@H](OC)[C@H](O)CC3)=O)=O)O2)=O)=O)CCCC1)O | ||
| 分子式 | C51H79NO13 | 分子量 | 914.17 |
| 溶解度 | Soluble in DMSO | 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 | 1.0939 mL | 5.4694 mL | 10.9389 mL |
| 5 mM | 0.2188 mL | 1.0939 mL | 2.1878 mL |
| 10 mM | 0.1094 mL | 0.5469 mL | 1.0939 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。
Rapamycin allosterically inhibits the proteasome
Mol Pharmacol 2013 Jul;84(1):104-13.PMID:23619386DOI:10.1124/mol.112.083873.
Rapamycin is a canonical allosteric inhibitor of the mammalian tarpet of rapamycin (mTOR) kinase with immunosuppressive and proapoptotic activities. We found that in vitro rapamycin also regulates the proteasome, which is an essential intracellular protease of the ubiquitin-proteasome pathway. Rapamycin inhibits proteinase and selected peptidase activities of the catalytic core proteasome at low micromolar concentrations. Moreover, the drug interferes with binding of the 19S cap essential for processing of polyubiquitinylated substrates and with the PA200 proteasome activator to the 20S catalytic core proteasome. These protein complexes are known to bind to specific grooves on the α face region of the 20S core. Treatment with rapamycin affects the conformational dynamics of the proteasomal gate, which is centrally positioned within the α face and allosterically regulated element responsible for the intake of substrates. We showed that rapamycin shares all the proteasome targeting properties not only with other two-domain, closed-ring analogs (rapalogs) but also with its single domain mimics and Seco-Rapamycin, which is the first in vivo open-ring metabolite of rapamycin that does not affect mTOR. We hypothesize that rapamycin and related compounds bind to the α face and allosterically impact proteasome function. This article discusses the implications of our findings for the mechanism of in vivo actions of rapamycin and for the design of novel allosteric drugs targeting the proteasome.