CC-115 hydrochloride
目录号 : GC34121
A dual inhibitor of mTOR and DNA-PK
Cas No.:1300118-55-1
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
|
Kinase experiment: |
An HTR-FRET substrate phosphorylation assay is employed for mTOR kinase. PI3Kα IC50 determinations are outsourced using the mobility shift assay format. Compounds (e.g., CC-115) are assessed against concentrations of ATP at approximately the Km for the assay, with average ATP Km of 15 μM and 50 μM for the mTOR and PI3K assays, respectively[1]. |
|
Cell experiment: |
PC-3 cells are cultured in growth media. For biomarker studies cells are treated for 1 h and then assayed for pS6 and pAkt levels using MesoScale technology. For proliferation experiments, cells are treated with compound (e.g., CC-115) and then allowed to grow for 72 h. All data are normalized and represented as a percentage of the DMSO-treated cells. Results are then expressed as IC50 values[1]. |
|
Animal experiment: |
Mice[1]Encouraged by the observed exposures, CC-115 is advanced into single dose PK/PD studies assessing mTOR pathway biomarker inhibition in tumor bearing mice. PC-3 tumor-bearing mice are administered with a single dose of CC-115, dosed orally at either 1 or 10 mg/kg, and plasma and tumor samples are collected at various time points for analysis. Significant inhibition of both mTORC1 (pS6) and mTORC2 (pAktS473) is observed for all compounds and the level of biomarker inhibition correlated to plasma compound levels. |
|
References: [1]. Mortensen DS, et al. Optimization of a Series of Triazole Containing Mammalian Target of Rapamycin (mTOR) Kinase Inhibitors and the Discovery of CC-115. J Med Chem. 2015 Jul 23;58(14):5599-5608. |
|
CC-115 is a dual inhibitor of mammalian target of rapamycin (mTOR) and DNA protein kinase (DNA-PK; IC50s = 0.021 and 0.013 ?M, respectively).1,2 It is selective for mTOR and DNA-PK over PI3Kα, ATM, and ATR (IC50s = 0.85, >30, and >30 ?M, respectively). CC-115 inhibits growth in a panel of 123 cancer cell lines, including breast, head and neck, and lung cancer cells (GI50s = 0.015-1.77 ?M), and non-homologous end joining (NHEJ) in CAL-51 and MDA-MB-231 breast, PC3 prostate, and HCT116 colon cancer cells (IC50s = 3.15, 2.16, 2.72, and 6.35 ?M, respectively).2 It reduces tumor growth in a PC3 prostate cancer mouse xenograft model when administered at doses of 0.25, 0.5, and 1 mg/kg twice per day.1
1.Mortensen, D.S., Perrin-Ninkovic, S.M., Shevlin, G., et al.Optimization of a series of triazole containing mammalian target of rapamycin (mTOR) kinase inhibitors and the discovery of CC-115J. Med. Chem.58(14)5599-5608(2015) 2.Tsuji, T., Sapinoso, L.M., Tran, T., et al.CC-115, a dual inhibitor of mTOR kinase and DNA-PK, blocks DNA damage repair pathways and selectively inhibits ATM-deficient cell growth in vitroOncotarget8(43)74688-74702(2017)
| Cas No. | 1300118-55-1 | SDF | |
| Canonical SMILES | [H]Cl.O=C1CN=C2C(N1CC)=NC(C3=C(C)N=C(C4=NN=CN4)C=C3)=CN2 | ||
| 分子式 | C16H17ClN8O | 分子量 | 372.81 |
| 溶解度 | DMSO : ≥ 30 mg/mL (80.47 mM) | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.6823 mL | 13.4117 mL | 26.8233 mL |
| 5 mM | 0.5365 mL | 2.6823 mL | 5.3647 mL |
| 10 mM | 0.2682 mL | 1.3412 mL | 2.6823 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。