1-Imidazo[1,2-a]pyridin-6-yl-ethylamine cas 1270475-03-0

· CAS Number: 1270475-03-0
· Chemical Name: (E)-N-(4-(3-pyridyl)pyrimidin-2-yl)-4-(((4-(ethylsulfonyl)phenyl)amino)methyl)benzoylamide
· Common Code: PF-06463922
· Main Targets: ALK (Anaplastic Lymphoma Kinase) and ROS1
· R&D Company: Pfizer
· Commercial Name: Lorbrena® (Lorlatinib)
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Detailed Explanation
What is it?
PF-06463922 (Lorlatinib) is a potent, selective, and brain-permeable small molecule kinase inhibitor. It is designed to target two specific tyrosine kinases: ALK and ROS1. These kinases undergo genetic mutations or rearrangements in certain types of cancers, driving the growth and survival of tumors.
2. Mechanism of Action
Lorlatinib exerts its effects in the following ways:
· ATP competitive inhibition: It binds to the ATP binding sites of ALK and ROS1 kinases, preventing them from obtaining phosphate groups.
· Blocking signal transduction: This inhibits the activity of the kinases, thereby interrupting the downstream signaling pathways that promote cell proliferation and survival.
· Inducing cell apoptosis: Ultimately, this leads to the programmed death of cancer cells.
3. Key Features and Advantages
· Broad-spectrum anti-mutation activity: This is the most prominent feature of lorlatinib. It is designed to overcome resistance mutations to the first-generation (such as crizotinib) and second-generation (such as alectinib, ceritinib) ALK inhibitors. It is effective against most known ALK resistance mutations, especially the most challenging G1202R mutation.
· High blood-brain barrier penetration: The molecular structure of lorlatinib has been optimized to enable efficient penetration of the blood-brain barrier. This is crucial for treating ALK-positive non-small cell lung cancer (NSCLC), as this disease often involves brain metastases. Its strong central nervous system activity makes it outstanding in preventing and treating brain metastases.
· Dual-target inhibition: In addition to ALK, it can also effectively inhibit tumors with ROS1 rearrangement, providing treatment options for another group of lung cancer patients.
4. Clinical Application
Lorlatinib has been approved for marketing in multiple countries and regions including the United States, China, the European Union, etc., and its commercial name is Lorbrena® (Lorlatinib).
· Main indications:
· It is used to treat adult patients with ALK-positive metastatic non-small cell lung cancer who have experienced disease progression after treatment with first-generation or second-generation ALK inhibitors.
· In some cases, it is also used as the first-line treatment for ALK-positive NSCLC.
· Efficacy: Clinical studies have shown that lorlatinib can produce significant and durable therapeutic responses in patients with ALK-positive NSCLC who have failed multiple lines of treatment, especially those with brain metastases.
5. Chemical Information (Summary)
· Molecular formula: C₂₁H₁₉FN₆O₂
· Molecular weight: 406.41 g/mol
· Appearance: Usually a white to off-white solid powder.
· Storage: It should be stored at room temperature, in a dry place and protected from light.
Summary

CAS 1270475-03-0 (Lorlatinib) is not merely an ordinary chemical substance; it represents a significant milestone in the field of targeted cancer treatment. As a third-generation ALK inhibitor, it overcomes the main limitations of previous drugs - drug resistance and brain metastasis. Its success highlights the powerful role of rational drug design based on structure in the development of new and more effective therapies, providing new hope and opportunities for prolonging life for many patients with ALK-positive lung cancer.