WF-47-JS03
目录号 : GC61381
WF-47-JS03是一种有效的选择性RET激酶抑制剂，比对激酶插入域受体(KDR)的选择性高500多倍。WF-47-JS03作用于转染KIF5B-RET的Ba/F3细胞和转染CCDC6-RET的LC-2/ad肺癌细胞，IC50分别为1.7nM和5.3nM。可透过血脑屏障。
Cas No.:2561413-77-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
WF-47-JS03 is a potent and selective RET kinase inhibitor with IC50s of 1.7 nM and 5.3 nM for KIF5B-RET transfected Ba/F3 cells, CCDC6-RET transfected LC-2/ad lung cancer cells, respectively. WF-47-JS03 demonstrates >500-fold selectivity against kinase insert domain receptor (KDR). Effective brain penetration[1].
WF-47-JS03 inhibits Tel-KDR transfected Ba/F3 cells, and Ba/F3 wild-type cell lines with IC50s of 0.99 and 1.5 μM, respectively[1].
WF-47-JS03 significantly inhibits tumor growth in RIE KIF5B-RET xenograft mice and is well tolerated at 1, 3, and 10 mg/kg in the 10 day study[1]. Animal Model: Female 6-8 week old Harlan Foxn1 nude mice with RIE-RET-KIF5B transgenic cell line
[1]. Casey J N Mathison , et al. Efficacy and Tolerability of Pyrazolo[1,5- a]pyrimidine RET Kinase Inhibitors for the Treatment of Lung Adenocarcinoma. ACS Med Chem Lett. 2020 Feb 12;11(4):558-565.
| Cas No. | 2561413-77-0 | SDF | |
| Canonical SMILES | NC(N1C(N=C2NC3CC(C)(C)N(C)C(C)(C)C3)=C(C4=CC(OC)=C(OC)C=C4)C=N1)=C2C5=CC=CC=C5 | ||
| 分子式 | C30H38N6O2 | 分子量 | 514.66 |
| 溶解度 | 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 | 1.943 mL | 9.7152 mL | 19.4303 mL |
| 5 mM | 0.3886 mL | 1.943 mL | 3.8861 mL |
| 10 mM | 0.1943 mL | 0.9715 mL | 1.943 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。
Efficacy and Tolerability of Pyrazolo[1,5- a]pyrimidine RET Kinase Inhibitors for the Treatment of Lung Adenocarcinoma
ACS Med Chem Lett 2020 Feb 12;11(4):558-565.PMID:32292564DOI:PMC7153282
RET (REarranged during Transfection) kinase gain-of-function aberrancies have been identified as potential oncogenic drivers in lung adenocarcinoma, along with several other cancer types, prompting the discovery and assessment of selective inhibitors. Internal mining and analysis of relevant kinase data informed the decision to investigate a pyrazolo[1,5-a]pyrimidine scaffold, where subsequent optimization led to the identification of compound WF-47-JS03 (1), a potent RET kinase inhibitor with >500-fold selectivity against KDR (Kinase insert Domain Receptor) in cellular assays. In subsequent mouse in vivo studies, compound 1 demonstrated effective brain penetration and was found to induce strong regression of RET-driven tumor xenografts at a well-tolerated dose (10 mg/kg, po, qd). Higher doses of 1, however, were poorly tolerated in mice, similar to other pyrazolo[1,5-a]pyrimidine compounds at or near the efficacious dose, and indicative of the narrow therapeutic windows seen with this scaffold.