产品说明书
Lorlatinib
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同义名 : | PF-06463922;PF-6463922 |
| CAS号 : | 1454846-35-5 | |
| 货号 : | A231019 | |
| 分子式 : | C21H19FN6O2 | |
| 纯度 : | 98% | |
| 分子量 : | 406.413 | |
| MDL号 : | - | |
| 存储条件： |
粉末 Sealed in dry,Store in freezer, under -20°C 液体 -20°C:3-6个月-80°C:12个月 |
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| 溶解度 : |
DMSO: 30 mg/mL(73.82 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO |
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| 动物实验配方： |
IP 2% DMSO+2% Tween80+40% PEG300+water 10 mg/mL clear PO 0.5% CMC-Na 30 mg/mL suspension |
| 生物活性 | |||
|---|---|---|---|
| 靶点 |
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| 描述 | ALK (anaplastic lymphoma kinase) is a tyrosine kinase that is constitutively activated in certain cancers, following gene alterations such as chromosomal translocation, amplification or point mutation. Lorlatinib is a dual inhibitor of ALK and ROS1 with Ki values of 2nM, 7nM and 70nM for ROS1, ALK and ALK-L1196M (measured by kinase screening assays). Cellular study showed that Lorlatinib possessed a more potent kinase inhibitory effect on EML4-ALK mutation, compared with Crizotinib, with IC50 values on p-ALK of 1.3nM, 0.2nM, 1.6nM, 15nM, 4.2nM, 21nM, 9nM, 77nM and 38nM for different mutations ALK, F1174L, C1156Y, G1269A, S1206Y, L1196M, L1152R, G1202R and 1151Tins in 3T3-EML4-ALK engineered cell lines[1]. As a dual inhibitor, Lorlatinib also showed potency to block crizotinib-resistant ROS1 mutations. In vitro study showed that Lorlatinib exhibited subnanomolar IC50 values of ranging in 0.19–0.53nM against pROS1-Tyr2274 in a panel of NIH 3T3 and BaF3 cells engineered to express selected oncogenic ROS1 fusion variants including CD74-ROS1, SLC34A2-ROS1, and FIGROS1. Also, it inhibited the crizotinib-refractory ROS1-G2032R mutation and the ROS1-G2026M gatekeeper mutation. In vivo studies showed that Lorlatinib markedly inhibit the tumor growth in models expressing FIG-ROS1 (1, 3mg/kg), CD74-ROS1 (0.2-6mg/kg) and the CD74-ROS1-G2032R (3-60mg/kg) mutation[2]. In addition, Lorlatinib is designed for CNS availability for a single 10mg/kg oral dose of this compound achieved its distributes into the CNS in rat[1]. Lorlatinib at dose of 10mg/kg (but administered by s.c. osmotic pumps) demonstrated the antitumor activity in a genetically engineered mouse model of FIG-ROS1 glioblastoma[2]. | ||
| 作用机制 | Lorlatinib is an ATP-competitive small-molecule inhibitor.[2] | ||
| 细胞研究 | |||||
|---|---|---|---|---|---|
| 细胞系 | 浓度 | 检测类型 | 检测时间 | 活动说明 | 数据源 |
| mouse NIH-3T3 cells | Function assay | 1 h | Inhibition of human EML4-fused ALK F1174L mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA | 24819116 | |
| 实验方案 | |||
|---|---|---|---|
| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
2.46mL 0.49mL 0.25mL |
12.30mL 2.46mL 1.23mL |
24.61mL 4.92mL 2.46mL |
