CC-223
(Synonyms: CC-223; ATG-008) 目录号 : GC13648
A potent, selective inhibitor of mTOR
Cas No.:1228013-30-6
Sample solution is provided at 25 µL, 10mM.
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IC50: 16 nM
CC-223 is an orally bioavailable mTOR inhibitor.
The mammalian target of rapamycin (mTOR) pathway is critical for tumor development, and mTOR inhibitors have revealed modest results.
In vitro: CC-223 was identified as an ATP–competitive inhibitor of the mTOR kinase targeting mTORC1 of both 4EBP1 and p70 S6 kinase 1 and mTORC2, which prevented the upregulation of AKT phosphorylation. Moreover, CC-223 was selectively potent to mTOR kinase while showed more than 150-fold sensitivity against the related lipid kinase, PI3Ka. In addition, CC-223 was active over many non-Hodgkin lymphoma cell lines and solid tumor lines such as including glioma, breast, hepatocellular carcinoma, as well as non–small cell lung cancer [1].
In vivo: In animal study, CC-223 was selected for evaluation in PC-3 tumor bearing efficacy mouse models. Mice were orally treated with vehicle or various doses of CC-223 once daily or twice daily at a dose of 5 mL/kg for 21 days, and the final reductions of tumor volume were measured following the final day of dosing. Results showed that All CC-223 had dose- and schedule-dependent inhibition of tumor growth in the PC-3 model. Moreover, the maximum observed efficacy for CC-223 was determined to be 87%, at its tolerated dose of 25 mg/kg q.d. [1].
Clinical trial: In previous clinical study, CC-223 was found to be tolerable with manageable toxicities. In addition, the preliminary antitumor activity, such as tumor regression and evidence of mTORC1/mTORC2 pathway inhibition were also observed [2].
References:
[1] Mortensen DS, et al. Discovery of Mammalian Target of Rapamycin (mTOR) Kinase Inhibitor CC-223. J Med Chem. 2015 Jul 9;58(13):5323-5333.
[2] Bendell JC, et al. A phase I dose-escalation study to assess safety, tolerability, pharmacokinetics, and preliminary efficacy of the dual mTORC1/mTORC2 kinase inhibitor CC-223 in patients with advanced solid tumors or multiple myeloma. Cancer. 2015 Oct 1;121(19):3481-90.
Kinase experiment: | Counter screen against 246 protein kinases is outsourced and completed at a fixed CC-223 concentration (10 μM). Follow-up IC50 value determinations for ephrin type-B receptor 3 kinase (EPHB3), colony stimulating factor 1 receptor tyrosine kinase (CSF1R or cFMS), and FMS-related tyrosine kinase 4 (FLT4) are outsourced to Invitrogen[1]. |
Cell experiment: | For other cell panel proliferation assays, CC-223 (1 nM, 100 nM and 1 μM) is spotted via an acoustic dispenser (EDC ATS-100) into an empty 384-well plate. Cells are diluted to desired densities and added directly to the compound-spotted plates. Cells are allowed to grow for 72 hours. Viability is assessed via Cell Titer-Glo. All data are normalized and represented as a percentage of the DMSO-treated cells. Results are then expressed as GI50 and/or IC50 values[1]. |
Animal experiment: | Mice[1]Female 6- to 8-weeks-old CB17 SCID mice are inoculated s.c. with 2×106 PC-3 cells. When tumors reach approximately 125 mm3, mice are randomized and treated once daily, twice daily, or every 2 days orally with vehicle or various doses of CC-223, at a dose volume of 5 mL/kg. The twice-daily doses are administered with a 10 hours separation between the morning and evening doses. Tumor volumes are determined before the initiation of treatment and are considered as the starting volumes. Tumors are measured twice a week for the duration of the study. The long and short axes of each tumor are measured using a digital caliper in millimeters. The tumor volumes are calculated. The tumor volumes are expressed in cubic millimeters (mm3). |
References: [1]. Mortensen DS, et al. CC-223, a Potent and Selective Inhibitor of mTOR Kinase: In Vitro and In Vivo Characterization. Mol Cancer Ther. 2015 Jun;14(6):1295-305. | |
| Cas No. | 1228013-30-6 | SDF | |
| 别名 | CC-223; ATG-008 | ||
| 化学名 | 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((1r,4r)-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one | ||
| Canonical SMILES | O=C1N([C@H]2CC[C@H](OC)CC2)C3=NC(C4=CN=C(C(O)(C)C)C=C4)=CN=C3NC1 | ||
| 分子式 | C21H27N5O3 | 分子量 | 397.47 |
| 溶解度 | DMF: 30 mg/mL,DMF:PBS(pH 7.2)(1:1): 0.5 mg/mL,DMSO: 25 mg/mL,Ethanol: 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 | 2.5159 mL | 12.5796 mL | 25.1591 mL |
| 5 mM | 0.5032 mL | 2.5159 mL | 5.0318 mL |
| 10 mM | 0.2516 mL | 1.258 mL | 2.5159 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。
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet