Brigatinib
(Synonyms: 布格替尼; AP-26113) 目录号 : GC19084
An orally bioavailable ALK inhibitor
Cas No.:1197953-54-0
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');)
;)
Brigatinib is a highly potent and selective ALK inhibitor, with an IC50 of 0.6 nM.
Brigatinib potently inhibits the in vitro kinase activity of ALK (IC50, 0.6 nM) and all five mutant variants tested, including G1202R (IC50, 0.6-6.6 nM). Brigatinib demonstrates a high degree of selectivity, only inhibiting 11 additional native or mutant kinases with IC50 1000 nM). In cellular assays, brigatinib inhibits ALK and ROS1 with IC50s of 14 and 18 nM, respectively. Brigatinib inhibits FLT3 and IGF-1R with about 11-fold lower potency (IC50, 148-158 nM) and inhibits mutant variants of FLT3 and EGFR with 15- to 35-fold lower potency (IC50, 211-489 nM). Brigatinib inhibits cell growth with GI50 values ranging from 503 to 2,387 nM in three ALK-negative ALCL and NSCLC cell lines[1]. Brigatinib inhibits ALK activity and abrogates proliferation of ALK addicted neuroblastoma cell lines, with IC50 of 75.27 ± 8.89 nM. Brigatinib inhibits both the ALK-I1171N and the ALK-G1269A mutant receptors at 10 and 4 nM levels, respectively[3].
Brigatinib (10, 25, or 50 mg/kg once daily, p.o.) leads to a dose-dependent inhibition of tumor growth in ALK+ Karpas-299 (ALCL) and H2228 (NSCLC) xenograft mouse models. Brigatinib markedly enhances survival of mice bearing ALK+ brain tumors compared with crizotinib[1]. Brigatinib (10, 25, 50 mg/kg, p.o.) results in dose-dependent antitumor activity, with tumor regressions in a mouse model of NSCLC[2].
References:
[1]. Zhang S, et al. The Potent ALK Inhibitor Brigatinib (AP26113) Overcomes Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in Preclinical Models. Clin Cancer Res. 2016 Nov 15;22(22):5527-5538
[2]. Huang WS, et al. Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase. J Med Chem. 2016 May 26;59(10):4948-64.
[3]. Siaw JT, et al. Brigatinib, an anaplastic lymphoma kinase inhibitor, abrogates activity and growth in ALK-positive neuroblastoma cells, Drosophila and mice. Oncotarget. 2016 May 17;7(20):29011-22
|
Kinase experiment: |
In vitro HotSpotSM kinase profiling of 289 kinases is performed. The assay is conducted in the presence of 10 μM [33P]-ATP, using brigatinib concentrations ranging from 0.05 nM to 1 μM. |
|
Cell experiment: |
Cells are seeded at 15,000 per well with serial dilutions of the indicated inhibitors. After 72 hours cell viability is assessed by resazurin. IC50 values are calculated with GraphPad Prism 6.0 by fitting data to a log (inhibitor concentration) vs. normalized response (variable slope) equation. Each experiment is performed in duplicate and repeated at least three times. |
|
Animal experiment: |
Mice: (1) Eight- to 10-week-old female SCID/beige mice are injected intravenously with 5×106 H3122 cells per mouse and are randomly selected into treatment groups (n=10) when the average tumor size reaches appr 300 mm3 (day zero). Treatments are administered orally for up to 21 consecutive days at a 10 mL/kg dose volume. Subcutaneous tumors are measured two or three times weekly. Tumor volume (in mm3) is calculated using the formula (L×W2)/2. When a tumor reaches 10% of the body weight of the host, the animal is euthanized via CO2 asphyxiation. (2) Eight- to 10-week old female SCID/beige mice are injected subcutaneously with 2.5×106 Karpas-299 cells per mouse and are randomly selected into treatment groups (n=10) when the average tumor size reached appr 180 mm3 (day zero). Treatments are administered orally for 14 consecutive days at a 10 mL/kg dose volume. Tumor volume is measured and calculated as described for the H3122 model. |
|
References: [1]. Zhang S, et al. The Potent ALK Inhibitor Brigatinib (AP26113) Overcomes Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in Preclinical Models. Clin Cancer Res. 2016 Nov 15;22(22):5527-5538 |
|
| Cas No. | 1197953-54-0 | SDF | |
| 别名 | 布格替尼; AP-26113 | ||
| Canonical SMILES | CN1CCN(C2CCN(C3=CC=C(NC4=NC=C(Cl)C(NC5=CC=CC=C5P(C)(C)=O)=N4)C(OC)=C3)CC2)CC1 | ||
| 分子式 | C29H39ClN7O2P | 分子量 | 584.09 |
| 溶解度 | Ethanol : 10 mg/mL (17.12 mM);DMSO : 2 mg/mL (3.42 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 | 1.7121 mL | 8.5603 mL | 17.1206 mL |
| 5 mM | 0.3424 mL | 1.7121 mL | 3.4241 mL |
| 10 mM | 0.1712 mL | 0.856 mL | 1.7121 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