DL001
目录号 : GC35874
DL001 是一种依赖于 FKBP12 的雷帕霉素类似物，选择性的 mTORC1 抑制剂，IC50 为 74.9 pM。 在细胞系中，DL001 有效抑制升高的 mTORC1 活性并恢复正常基因表达至缺乏功能性结节性硬化症复合体的细胞。在 C57BL/6J 小鼠体内，DL001 抑制 mTORC1 信号传导，但不影响葡萄糖体内平衡，并且显着降低脂质代谢和体内免疫系统而没有其他副作用。
Cas No.:909387-87-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
DL001, a FKBP12-dependent rapamycin analog, is a selective mechanistic Target Of Rapamycin Complex 1 (mTORC1) inhibitor with an IC50 of 74.9 pM. In cells, DL001 efficiently represses elevated mTORC1 activity and restores normal gene expression to cells lacking a functional tuberous sclerosis complex. DL001 inhibits mTORC1 signaling without impairing glucose homeostasis and with substantially reduced and no side effects on lipid metabolism and the immune system in vivo in C57BL/6J mice[1]. mTORC1|74.9 pM (IC50)
[1]. Schreiber KH , et al. A novel rapamycin analog is highly selective for mTORC1 in vivo. Nat Commun. 2019 Jul 19;10(1):3194.
| Cas No. | 909387-87-7 | SDF | |
| Canonical SMILES | O[C@@H]1CC[C@@H](C[C@@H](C)[C@H](CC([C@H](C)/C=C(C)/[C@@H](O)[C@H]2O)=O)OC([C@@H]3CCCCN3C(C([C@]4(O)O[C@H](C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C2=O)CC[C@H]4C)=O)=O)=O)CC1 | ||
| 分子式 | C49H75NO12 | 分子量 | 870.12 |
| 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 | 1.1493 mL | 5.7463 mL | 11.4927 mL |
| 5 mM | 0.2299 mL | 1.1493 mL | 2.2985 mL |
| 10 mM | 0.1149 mL | 0.5746 mL | 1.1493 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。
A novel rapamycin analog is highly selective for mTORC1 in vivo
Nat Commun 2019 Jul 19;10(1):3194.PMID:31324799DOI:PMC6642166
Rapamycin, an inhibitor of mechanistic Target Of Rapamycin Complex 1 (mTORC1), extends lifespan and shows strong potential for the treatment of age-related diseases. However, rapamycin exerts metabolic and immunological side effects mediated by off-target inhibition of a second mTOR-containing complex, mTOR complex 2. Here, we report the identification of DL001, a FKBP12-dependent rapamycin analog 40x more selective for mTORC1 than rapamycin. DL001 inhibits mTORC1 in cell culture lines and in vivo in C57BL/6J mice, in which DL001 inhibits mTORC1 signaling without impairing glucose homeostasis and with substantially reduced or no side effects on lipid metabolism and the immune system. In cells, DL001 efficiently represses elevated mTORC1 activity and restores normal gene expression to cells lacking a functional tuberous sclerosis complex. Our results demonstrate that highly selective pharmacological inhibition of mTORC1 can be achieved in vivo, and that selective inhibition of mTORC1 significantly reduces the side effects associated with conventional rapalogs.