Lorlatinib

SKU: orb1304578

Description

Lorlatinib (PF-6463922) is a potent, orally bioavailable small molecule inhibitor targeting ALK and ROS1 tyrosine kinases. It is widely used in preclinical oncology research to investigate resistance mechanisms and evaluate antitumor efficacy in both cellular assays and animal models of non-small cell lung cancer.

Research Area

Cardiovascular Research, Cell Biology, Immunology & Inflammation, Signal Transduction

Key Properties

• CAS Number: 1454846-35-5
• MW: 406.41
• Purity: 99.95%
• Formula: C₂₁H₁₉FN₆O₂
• SMILES: C[C@H]1Oc2cc(cnc2N)-c2c(CN(C)C(=O)c3ccc(F)cc13)nn(C)c2C#N
• Target: ALK,ROS,Tyrosine Kinases,Apoptosis,ROS Kinase
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.92 mM);Ethanol:40.6 mg/mL (99.9 mM);DMSO:13 mg/mL (31.99 mM)

Bioactivity

• Target IC50:
  TYK1/LTK:2.7 nM|ALK:<0.07 nM(Ki)|ROS1:<0.02 nM(Ki)|ALK (L1196M):0.07 nM(Ki)|FER:3.3 nM
• In Vivo:
  In NIH3T3 xenograft models expressing human CD74-ROS1 and Fig-ROS1, PF-06463922 inhibits cell proliferation by repressing ROS1 phosphorylation and downstream signaling molecules, including Cyclin D1. Furthermore, PF-06463922 demonstrates significant antitumor activity in mice bearing tumor grafts that overexpress EML4-ALK, EML4-ALK-L1196M, EML4-ALK-G1269A, EML4-ALK-G1202R, or NPM-ALK.
• In Vitro:
  PF-06463922 effectively inhibits cell proliferation and induces apoptosis in HCC78 human NSCLC cells containing SLC34A2-ROS1 fusions and in BaF3-CD74-ROS1 cells expressing human CD74-ROS1. It also demonstrates this inhibitory action on cell proliferation and induces apoptosis in NSCLC cells with either non-mutated or mutated ALK fusions. PF-06463922 exhibits significant cellular activity against ALK and a wide range of ALK clinical mutations (IC50=0.2-77 nM).
• Cell Research:
  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.

Storage & Handling

• Storage: keep away from moisture,store under nitrogen,store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Cluster of differentiation 246, CD246, ALK, ALK (L1196M), ALK tyrosine kinase receptor, Anaplastic lymphoma kinase, Anaplastic lymphoma kinase (ALK), Apoptosis, brain-penetrant, Carcinoma, NSCLC, Neuroblastoma, LTK (TYK1), Lorlatinib, Loratinib, kinase, inhibit, mutation, Inhibitor, PF-6463922, PF6463922, PF 6463922, PF06463922, PF-06463922, PF 06463922, third-generation, ROS, ROS1, ROSKinase, ROS Kinase, TyrosineKinases, Tyrosine Kinases, tyrosine

Compound Identifiers

PubChem CID

71731823