GDC-0152
(Synonyms: GDC0152, GDC 0152) 目录号 : GC14451
An inhibitor of IAPs
Cas No.:873652-48-3
Sample solution is provided at 25 µL, 10mM.
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GDC-0152 is a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins, including ML-IAP, XIAP, cIAP1 and cIAP2, that binds to the BIR domain of ML-IAP and the BIR3 domains of XIAP, cIAP1 and cIAP2 with values of inhibition constant Ki of 14 nM, 28 nM, 17 nM and 43 nM respectively. GDC-0152 potentially inhibits tumor growth of breast cancer by promoting cIAP1 degradation and inducing caspase-3/7 activation which result in the decreasing of cell viability of breast cancer cells with normal epithelial cells unaffected. In recent studies, GDC-0152 shows its ability to disrupt the binding of XIAP to caspase-9 and the association of ML-IAP, cIAP1 and cIAP2 with Smac in HEK293T cells.
Reference
[1].Flygare JA, Beresini M, Budha N, Chan H, Chan IT, Cheeti S, Cohen F, Deshayes K, Doerner K, Eckhardt SG, Elliott LO, Feng B, Franklin MC, Reisner SF, Gazzard L, Halladay J, Hymowitz SG, La H, LoRusso P, Maurer B, Murray L, Plise E, Quan C, Stephan JP, Young SG, Tom J, Tsui V, Um J, Varfolomeev E, Vucic D, Wagner AJ, Wallweber HJ, Wang L, Ware J, Wen Z, Wong H, Wong JM, Wong M, Wong S, Yu R, Zobel K, Fairbrother WJ. Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical candidate for the treatment of cancer (GDC-0152). J Med Chem. 2012;55(9):4101-4113
| Kinase experiment [1]: | |
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Fluorescence polarization-based competition assay |
Inhibition constants ( Ki ) for the antagonists are determined by adding the IAP protein constructs to wells containing serial dilutions of the antagonists or the peptide AVPW, and the Hid-FAM probe or AVP-diPhe-FAM probe, as appropriate, in the polarization buffer. Samples are read after a 30-min incubation. Fluorescence polarization values are plotted as a function of the antagonist concentration, and the IC50 values are obtained by fitting the data to a 4-parameter equation using KaleidaGraph software. Ki values for the antagonists are determined from the IC50 values. |
| Cell experiment [1, 2]: | |
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Cell lines |
U87MG, GL261, GBM6, GBM9 cell lines, and MDA-MB-231 breast carcinoma cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
1μM or 100μM; 72h or 8 days; 10 nM-10μM; 3h-24h |
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Applications |
GDC-0152 treatment triggered apoptosis and decreased IAP protein expression in glioblastoma cell lines. Moreover, GDC-0152 (10 nM-10μM) dose-dependently promoted degradation of cIAP1, induced caspase-3/7 activation, and lead to decreased viability of breast cancer cells. |
| Animal experiment [1, 2]: | |
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Animal models |
100 000 U87MG-iRFP cells were injected into the corpus callosum of athymic nude mice; MDA-MB-231 breast cancer xenograft model; |
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Dosage form |
10, 20, 50, and 100 mg/kg; intravenous injection or oral gavage; weekly for 2 months |
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Applications |
GDC-0152 (10 mg/kg or 20 mg/kg) dose-dependently increased survival and slowed down tumor growth of mice bearing intracranial tumors. Moreover, GDC-0152 (10, 50, and 100 mg/kg) suppressed tumor growth in dose-dependent manner in the MDA-MB-231 breast cancer xenograft model. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: 1. Flygare, J. A., Beresini, M., Budha, N., Chan, H., Chan, I. T., Cheeti, S., Cohen, F., Deshayes, K., Doerner, K., Eckhardt, S. G., Elliott, L. O., Feng, B., Franklin, M. C., Reisner, S. F., Gazzard, L., Halladay, J., Hymowitz, S. G., La, H., LoRusso, P., Maurer, B., Murray, L., Plise, E., Quan, C., Stephan, J. P., Young, S. G., Tom, J., Tsui, V., Um, J., Varfolomeev, E., Vucic, D., Wagner, A. J., Wallweber, H. J., Wang, L., Ware, J., Wen, Z., Wong, H., Wong, J. M., Wong, M., Wong, S., Yu, R., Zobel, K. and Fairbrother, W. J. (2012) Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical candidate for the treatment of cancer (GDC-0152). J Med Chem. 55, 4101-41132 2. Tchoghandjian, A., Souberan, A., Tabouret, E., Colin, C., Denicolai, E., Jiguet-Jiglaire, C., El-Battari, A., Villard, C., Baeza-Kallee, N. and Figarella-Branger, D. (2016) Inhibitor of apoptosis protein expression in glioblastomas and their in vitro and in vivo targeting by SMAC mimetic GDC-0152. Cell Death Dis. 7, e2325 | |
| Cas No. | 873652-48-3 | SDF | |
| 别名 | GDC0152, GDC 0152 | ||
| 化学名 | (2S)-1-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-N-(4-phenylthiadiazol-5-yl)pyrrolidine-2-carboxamide | ||
| Canonical SMILES | CC(C(=O)NC(C1CCCCC1)C(=O)N2CCCC2C(=O)NC3=C(N=NS3)C4=CC=CC=C4)NC | ||
| 分子式 | C25H34N6O3S | 分子量 | 498.64 |
| 溶解度 | ≥ 24.95 mg/mL in DMSO, ≥ 50.6 mg/mL in EtOH with ultrasonic and warming | 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.0055 mL | 10.0273 mL | 20.0545 mL |
| 5 mM | 0.4011 mL | 2.0055 mL | 4.0109 mL |
| 10 mM | 0.2005 mL | 1.0027 mL | 2.0055 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。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet