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Lorlatinib

Lorlatinib

产品编号 T3061   CAS 1454846-35-5
别名: 劳拉替尼, PF-6463922, PF-06463922, Loratinib

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。

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Lorlatinib Chemical Structure
Lorlatinib, CAS 1454846-35-5
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
其他形式的 Lorlatinib:
产品目录号及名称: Lorlatinib (T3061)
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选择批次  
纯度: 99.93%
纯度: 99.82%
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生物活性
化学信息
存储 & 溶解度
参考文献
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

存储

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度

Ethanol: 40.6 mg/mL (100 mM)

DMSO: 40.6 mg/mL (100 mM)

溶液配制表

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

计算器

摩尔浓度计算器
稀释计算器
配液计算器
分子量计算器
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输入分子式,点击计算,可计算出产品的分子量。

参考文献

1. Johnson TW, et al. J Med Chem. 2014, 57(11), 4720-4744. 2. Zou HY, et al. Mol Cancer Ther. 2013, 12, A277. 3. Zou HY, et al. Mol Cancer Ther. 2013, 12, C253. 4. Sparidans R W, Li W, Schinkel A H, et al. Bioanalytical liquid chromatography-tandem mass spectrometric assay for the quantification of the ALK inhibitors alectinib, brigatinib and lorlatinib in plasma and mouse tissue homogenates[J]. Journal of pharmaceutical and biomedical analysis. 2018 Nov 30;161:136-143. 5. Spatari, Claudia, et al. Bioanalytical assay for the quantification of the ALK inhibitor lorlatinib in mouse plasma using liquid chromatography-tandem mass spectrometry. Journal of Chromatography B. 2018 Apr 15;1083:204-208. 6. Wenlong Li, Rolf W. Sparidans, Yaogeng Wang, Maria C. Lebre, Jos H. Beijnen, and Alfred H. Schinkel. Oral coadministration of elacridar and ritonavir enhances brain accumulation and oral availability of the novel ALK/ROS1 inhibitor lorlatinib [J]. European Journal of Pharmaceutics and Biopharmaceutics. 2019 Mar;136:120-130. 7. Wenlong Li, Rolf W. Sparidans, Yaogeng Wang, Maria C. Lebre, Els Wagenaar, Jos H. Beijnen, and Alfred H. P-glycoprotein (MDR1/ABCB1) restricts brain accumulation and Cytochrome P450-3A (CYP3A) limits oral availability of the novel ALK/ROS1 inhibitor lorlatinib [J]. International journal of cancer. 2018 Oct 15;143(8):2029-2038.

文献引用

1. Li W, Sparidans R W, Wang Y, et al. P-glycoprotein (MDR1/ABCB1) restricts brain accumulation and Cytochrome P450-3A (CYP3A) limits oral availability of the novel ALK/ROS1 inhibitor lorlatinib. International Journal of Cancer. 2018, 143(8): 2029-2038 2. Li W, Sparidans R W, Wang Y, et al. Oral coadministration of elacridar and ritonavir enhances brain accumulation and oral availability of the novel ALK/ROS1 inhibitor lorlatinib. European Journal of Pharmaceutics and Biopharmaceutics. 2019, 136: 120-130 3. Spatari C, Li W, Schinkel A H, et al. Bioanalytical assay for the quantification of the ALK inhibitor lorlatinib in mouse plasma using liquid chromatography-tandem mass spectrometry. Journal of Chromatography B. 2018, 1083: 204-208 4. Sparidans R W, Li W, Schinkel A H, et al. Bioanalytical liquid chromatography-tandem mass spectrometric assay for the quantification of the ALK inhibitors alectinib, brigatinib and lorlatinib in plasma and mouse tissue homogenates. Journal of Pharmaceutical and Biomedical Analysis. 2018 Nov 30;161:136-143 5. Guan J, Borenäs M, Xiong J, et al.IGF1R Contributes to Cell Proliferation in ALK-Mutated Neuroblastoma with Preference for Activating the PI3K-AKT Signaling Pathway.Cancers.2023, 15(17): 4252.
Vidarabine Tyk2-IN-3 Ruxolitinib Delgocitinib ST271 Filgotinib Tafetinib ZAP-180013

相关化合物库

该产品包含在如下化合物库中:
酪氨酸激酶分子库 抗癌药物库 抗癌活性化合物库 抗癌上市药物库 抗癌临床化合物库 药物功能重定位化合物库 NO PAINS 化合物库 上市药物库 氧化还原化合物库 抑制剂库

剂量换算

对于不同动物的给药剂量换算,您也可以参考 更多...

体内实验配液计算器

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。

第一步:请输入动物实验的基本信息
剂量
mg/kg
每只动物体重
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给药体积
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动物数量
第二步:请输入动物体内配方组成,不同的产品配方组成不同,如有配方需求,可先联系我们提供正确的体内配方。
% DMSO
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% ddH2O
计算 重置

技术支持

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。

Keywords

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

 

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