The ALK Gene, An Attractive Target for Inhibitor Development
Carmen J. Tartari,
Anaplastic Lymphoma Kinase (ALK) is a receptor tyrosine kinase that belongs to the Insulin receptor subfamily involved as full length receptor in neural development. Even if the expression of ALK protein is down-regulated in the adults, the ALK full length is expressed in different types of tumors. Moreover, chromosomal rearrangements, involving the alk gene, can occur leading to the formation of different ALK fusion proteins characterized by the kinase domain of ALK fused to several partners that determine cellular localization. Structural investigation and characterization of the ALK kinase domain in absence of its crystal structure constituted the basis of development of ALK small molecule inhibitors. Here, we described normal function of the ALK receptor and its role in tumors; formation of the constitutively activated ALK fusion proteins and we reported an update of developed small molecule inhibitors of the ALK kinase activity.
Keywords: Anaplastic Lymphoma kinase (ALK), Modeling, Molecular targeting, Oncogenic fusion protein, Small molecule inhibitors, Targeted cancer therapy, tyrosine kinase, alk gene, constitutively activated ALK fusion proteins, non-Hodgkin's lymphoma, Immunohystochemical studies, pleiotrophin(PTN) and midkine (MK), histological defects, glioblastoma, breast cancer
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