BGB-102 (JNJ-26483327)
(Synonyms: 17-溴-1,8,9,10,11,12,13,14-八氢-20-甲氧基-13-甲基-4,6-乙烯桥嘧啶并[4,5-B][6,1,12]苯并氧杂二氮杂环十五碳七烯,JNJ-26483327) 目录号 : GC33172BGB-102 (JNJ-26483327) 是一种有效的多激酶抑制剂,针对 EGFR、HER2 和 HER4,IC50 分别为 9.6 nM、18 nM 和 40.3 nM。
Cas No.:807640-87-5
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | SKBR3 and BT474 cells are grown in 24-well plates after seeding approximately 20,000 cells per well. The cells are grown for at least 24 h before treatment with 40 µg/mL Herceptin, 5 µM JNJ-26483327, 10 µM TAPI-1, 10 µM ADAM17 inhibitor, or a combination of these drugs for different durations. For the exogenous ligand experiments, 100 ng/mL EGF, heregulin, or betacellulin is added to the cells in addition to Herceptin (40 µg/mL) for a total of 5 d in BT474 cells. On the day of the experiment, the cells are trypsinized and diluted with PBS. The viable cells are counted using a cell counter. |
Animal experiment: | Human BT474 breast tumour cells are injected directly into the inguinal region of the male NMRI Nude mice (1×107 cells/200 mL/animal) on day 0. On day 25, when the tumour volume has reached an approximate average of 200 mm3, mice are randomized according to tumour volume, with ten mice per treatment group. Mice are then treated twice daily with either vehicle (30% Captisol) or vehicle containing JNJ-26483327 (75 mg/kg twice daily) by gavage (p.o.) for 21 d. Alternatively, mice are treated twice weekly with either vehicle (0.9% [w/v] NaCl) or a vehicle containing Herceptin (10 mg/kg) by intraperitoneal injection administered in a volume of 10 mL/kg body weight, for three cycles (i.e., 21 d). Another group receives combined doses of both agents. Tumour size and body weights are measured twice weekly, with mice monitored daily for clinical signs of toxicity for the duration of the treatment. Clinical signs of toxicity included (but are not limited to) persistent anorexia or dehydration, morbidity, lethargy, hypothermia, and/or laboured respiration. |
References: [1]. Gijsen M, et al. HER2 phosphorylation is maintained by a PKB negative feedback loop in response to anti-HER2 herceptin in breast cancer. PLoS Biol. 2010 Dec 21;8(12):e1000563. |
BGB-102 is a potent multi-kinase inhibitor against EGFR, HER2, and HER4 with IC50s of 9.6 nM, 18 nM and 40.3 nM, respectively.
JNJ-26483327 (5 µM or 10 µM) with Herceptin treatment decreases HER2 phosphorylation in SKBR3 cells. JNJ-26483327 exerts greater inhibition of cell viability after 3, 6, or 8 d of treatment compared to Herceptin or JNJ-26483327 alone. JNJ-26483327 with TAPI-1 exerts less cell viability inhibition than Herceptin alone in both SKBR3 and BT474 cells[1].
JNJ-26483327 (75 mg/kg, p.o.) delays xenograft tumour growth compared to vehicle treatment, but when combines with Herceptin, they can abrogate the PKB feedback loop and is synergistic in inhibition of xenograft tumour growth[1].
[1]. Gijsen M, et al. HER2 phosphorylation is maintained by a PKB negative feedback loop in response to anti-HER2 herceptin in breast cancer. PLoS Biol. 2010 Dec 21;8(12):e1000563.
Cas No. | 807640-87-5 | SDF | |
别名 | 17-溴-1,8,9,10,11,12,13,14-八氢-20-甲氧基-13-甲基-4,6-乙烯桥嘧啶并[4,5-B][6,1,12]苯并氧杂二氮杂环十五碳七烯,JNJ-26483327 | ||
Canonical SMILES | CN1CCCCCOC(C(OC)=C2)=CC3=C2N=CN/C3=N\C4=CC(Br)=CC=C4C1 | ||
分子式 | C22H25BrN4O2 | 分子量 | 457.36 |
溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
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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 | 2.1865 mL | 10.9323 mL | 21.8646 mL |
5 mM | 0.4373 mL | 2.1865 mL | 4.3729 mL |
10 mM | 0.2186 mL | 1.0932 mL | 2.1865 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 | |||
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% DMSO % % Tween 80 % saline | ||||||||||
计算重置 |
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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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