Lorlatinib CAS NO.1454846-35-5

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Loratinib is an ALK inhibitor. ALK is a receptor tyrosine kinase that belongs to the insulin receptor superfamily and has a high degree of homology with leukocyte tyrosine kinase. In 1994, ALK was first discovered in anaplastic large-cell lymphoma (ALCL) in the form of the NPM1-ALK fusion gene. The ALK gene is located on human chromosome 2p23 and encodes a 1620 amino acid polypeptide. After post-translational modification, the ALK gene produces a mature ALK protein of 200-220kDa. ALK consists of an extracellular ligand binding domain, a transmembrane domain and an intracellular tyrosine kinase domain composed of 1030 amino acids. ALK is highly conserved in various species. ALK expressed in the adult brain is considered to play an important role in the development and function of the nervous system. ALK is also expressed in the small intestine, testis, prostate and colon, but it is expressed in normal lymphoid tissues, Not expressed in lung and other tissues. ALK can activate multiple intracellular signaling pathways, including phospholipase Cγ, JAK kinase, signal transducer and activator of transcription-3 (STAT3), phosphatidylinositol 3-kinase (PI3K), lactation Animal target of rapamycin (mammaliantargetofrapamycin, mTOR) and mitogen-activated protein kinase (MAPK) are involved in regulating cell growth, transformation and anti-apoptosis.

Loratinib should be regarded as a third-generation ALK inhibitor, which can inhibit 9 mutations of crizotinib resistance, has a strong blood-brain barrier permeability, and has a strong brain-entering effect. It is especially suitable for resistance to other ALKs. Of advanced NSCLC patients. Lauratinib carries EGFR sensitive mutations in advanced non-small cell lung cancer, which can be treated by many EGFR inhibitors, such as the first-generation drug Iressa, Tarceva, and Chemera, and the second-generation drug afatinib , Dacomitinib, the third-generation drug Ositinib (AZD9291)-these targeted drugs have an effective rate of up to 70% or even higher, with few side effects, and are the first choice for the treatment of such patients.