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GDC-0152

现货
Catalog No.
A4224
IAP 拮抗剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,400.00
现货
10mg
¥ 1,700.00
现货
50mg
¥ 5,700.00
现货
100mg
¥ 9,900.00
现货

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Background

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

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

文献引用

1. Jung H, Leal-Ekman JS, et al. "Atg14 protects the intestinal epithelium from TNF-triggered villus atrophy." Autophagy. 2019 Mar 20:1-12. PMID:30894050
2. Rosner A, Kravchenko O, et al. "IAP genes partake weighty roles in the astogeny and whole body regeneration in the colonial urochordate Botryllus schlosseri." Dev Biol. 2018 Oct 30. pii: S0012-1606(17)30904-1. PMID:30385275

Chemical Properties

StorageStore at -20°C
M.Wt498.64
Cas No.873652-48-3
FormulaC25H34N6O3S
SynonymsGDC0152, GDC 0152
Solubility≥24.95 mg/mL in DMSO, ≥50.6 mg/mL in EtOH with ultrasonic and warming, <2.44 mg/mL in H2O
Chemical Name(2S)-1-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-N-(4-phenylthiadiazol-5-yl)pyrrolidine-2-carboxamide
SDFDownload SDF
Canonical SMILESCC(C(=O)NC(C1CCCCC1)C(=O)N2CCCC2C(=O)NC3=C(N=NS3)C4=CC=CC=C4)NC
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

荧光偏振为基础的竞争分析

拮抗剂的抑制常数(Ki)通过以下方法测定:将IAP蛋白构建添加到含有不同稀释倍数的拮抗剂或AVPW肽中,将Hid-FAM探针或AVP-diPhe-FAM探针添加到偏振缓冲中。样品在孵育30分钟后读数。荧光偏振值是拮抗剂浓度的函数,并且IC50值是通过使用KaleidaGraph软件将数据拟合到4-参数方程获得。拮抗剂的Ki数值由IC50值确定。

细胞实验 [1, 2]:

细胞系

U87MG、GL261、GBM6、GBM9和MDA-MB-231乳腺癌细胞株

溶解方法

该化合物在DMSO中的溶解度> 10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应时间

1 μM或100 μM; 72 h或8 days; 10 nM-10 μM; 3 h-24 h

应用

GDC-0152诱导胶质母瘤细胞凋亡且减少细胞表达IAP蛋白。同时,GDC-0152 (10 nM-10 μM) 以剂量依赖的方式促进cIAP1蛋白降解、诱导caspase-3/7活化并且减少乳腺癌细胞的存活。

动物实验 [1, 2]:

动物模型

将10万数量的U87MG-iRFP细胞注射到无胸腺裸鼠的胼胝体而形成的肿瘤异种移植物; MDA-MB-231乳腺癌异种移植模型;

剂量

10、20、50或100 mg/kg; 静脉注射或口服; 每周一次、持续2个月

应用

GDC-0152 (10 mg/kg or 20 mg/kg)以剂量依赖的方式延长U87MG-iRFP瘤异种移植小鼠的生存时间并延缓肿瘤生长;同时,GDC-0152 (10、50或100 mg/kg) 以剂量相关的方式抑制MDA-MB-231乳腺癌异种移植模型的生长。

注意事项

请于室内测试所有化合物的溶解度。实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

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, 4101-4113

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

生物活性

Description GDC-0152是一种有效的小分子凋亡蛋白抑制因子(IAP )拮抗剂,作用于XIAP、ML-IAP、cIAP1和cIAP2的Ki值分别为28、14、17和43 nM。
靶点 XIAP ML-IAP cIAP1 cIAP2    
IC50 28 nM 14 nM 17 nM 43 nM    

质量控制

化学结构

GDC-0152

相关生物数据

GDC-0152