Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Lorlatinib (PF-6463922) 是一种具有口服活性,选择性,脑渗透性和 ATP 竞争性的ROS1/ALK 抑制剂,具有抗癌活性。它对 ROS1、野生型 ALK 和 ALKL1196M 的Ki 值分别为 <0.025 nM、<0.07 nM 和 0.7 nM。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 226 | 现货 | ||
2 mg | ¥ 313 | 现货 | ||
5 mg | ¥ 566 | 现货 | ||
10 mg | ¥ 917 | 现货 | ||
25 mg | ¥ 1,990 | 现货 | ||
50 mg | ¥ 2,890 | 现货 | ||
100 mg | ¥ 3,930 | 现货 | ||
1 g | ¥ 6,590 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 613 | 现货 |
产品描述 | Lorlatinib (PF-6463922) is an orally available, ATP-competitive inhibitor of the receptor tyrosine kinases, anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (Ros1), with potential antineoplastic activity. |
靶点活性 | ROS1:<0.02 nM(Ki), ALK:<0.07 nM(Ki), LTK (TYK1):2.7 nM, ALK (L1196M):0.07 nM(Ki), FER:3.3 nM |
体外活性 | 在表达人CD74-ROS1 和 Fig-ROS1的NIH3T3异种移植模型中,PF-06463922通过抑制ROS1磷酸化和下游信号分子,以及对周期蛋白D1的抑制发挥作用,能够抑制细胞增殖.在负荷肿瘤移植物,过表达EML4-ALK,EML4-ALK-L1196M,EML4-ALK-G1269A,EML4-ALK-G1202R 或NPM-ALK的小鼠体内,PF-06463922表现出明显的抗肿瘤活性. |
体内活性 | 在含有SLC34A2-ROS1 融合物的HCC78人NSCLC细胞和表达人CD74-ROS1的BaF3-CD74-ROS1细胞中,PF-06463922能够抑制细胞增殖,同时诱导细胞凋亡。在含有非突变型ALK或突变型ALK融合物的NSCLC 细胞中, PF-06463922能够抑制细胞增殖,同时诱导细胞凋亡。对ALK和大量ALK临床突变型(IC50=0.2 -77 nM), PF-06463922表现出明显的细胞活性。 |
激酶实验 | Recombinant human wild-type and mutant ALK kinase domain proteins (amino acids 1093–1411) are produced in-house using baculoviral expression, preactivated via autophosphorylation with MgATP, and assayed for kinase activity using a microfluidic mobility shift assay. The reactions contained 1.3 nM wild-type ALK or 0.5 nM mutant ALK (appropriate to produce 15-20% phosphorylation of peptide substrate after 1 h of reaction), 3 μM 5-FAM-KKSRGDYMTMQIG-CONH2), 5 mM MgCl2, and the Km level of ATP in 25 mM Hepes, pH 7.1. The inhibitors are shown to be ATP-competitive from kinetic and crystallographic studies. The Ki values are calculated by fitting the conversion (%) to a competitive inhibition equation. ROS1 enzyme is assayed as described above for ALK, except using 0.25 nM recombinant human ROS1 catalytic domain (amino acids 1883-2347). Kinase inhibitor selectivity is evaluated using a 206-kinase panel. |
细胞实验 | Cells are seeded in 96-well plates in growth medium containing 10% FBS and are cultured overnight at 37°C. The following day, serial dilutions of PF-06463922 or appropriate controls are added to the designated wells, and cells are incubated at 37°C for 72 h. A CellTiter-Glo assay is performed to determine the relative cell numbers. IC50 values are calculated by concentration-response curve fitting using a four-parameter analytical method. |
别名 | 劳拉替尼, PF-6463922, PF-06463922, Loratinib |
分子量 | 406.41 |
分子式 | C21H19FN6O2 |
CAS No. | 1454846-35-5 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Ethanol: 40.6 mg/mL (100 mM)
DMSO: 40.6 mg/mL (100 mM)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
Ethanol / DMSO | 1 mM | 2.4606 mL | 12.3028 mL | 24.6057 mL | 61.5142 mL |
5 mM | 0.4921 mL | 2.4606 mL | 4.9211 mL | 12.3028 mL | |
10 mM | 0.2461 mL | 1.2303 mL | 2.4606 mL | 6.1514 mL | |
20 mM | 0.123 mL | 0.6151 mL | 1.2303 mL | 3.0757 mL | |
50 mM | 0.0492 mL | 0.2461 mL | 0.4921 mL | 1.2303 mL | |
100 mM | 0.0246 mL | 0.123 mL | 0.2461 mL | 0.6151 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
Lorlatinib 1454846-35-5 Angiogenesis Apoptosis Immunology/Inflammation Tyrosine Kinase/Adaptors Tyrosine Kinases ROS ALK ROS Kinase ALK tyrosine kinase receptor Anaplastic lymphoma kinase PF 06463922 tyrosine inhibit Neuroblastoma Carcinoma 劳拉替尼 Anaplastic lymphoma kinase (ALK) NSCLC Inhibitor PF06463922 mutation PF 6463922 PF-6463922 kinase Cluster of differentiation 246 brain-penetrant CD246 PF-06463922 third-generation PF6463922 Loratinib inhibitor