ALK

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) that was first identified in anaplastic large cell lymphoma (ALCL) as part of the fusion protein NPM-ALK. ALK has been implicated in the pathogenesis of many types of cancer.

Products
Background
Literature
Gene Data

Inhibitors

Cat No Product Name / Activity
5310 ASP 3026
Potent anaplastic lymphoma kinase (ALK) inhibitor; also potent ACK inhibitor
4368 Crizotinib
Potent c-MET/ALK inhibitor
5111 GSK 1838705
Potent ALK inhibitor; also IR and IGF1R inhibitor
5098 KRCA 0008
Potent Ack1 and ALK dual inhibitor; orally bioavailable
5640 PF 06463922
High affinity and selective ALK and ROS1 inhibitor

Related Targets

    Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) that was first identified in anaplastic large cell lymphoma (ALCL) as part of the fusion protein NPM-ALK. ALK is highly expressed throughout the central and peripheral nervous system during development, with levels decreasing following gestation. Low levels of ALK protein are however, expressed in the adult CNS, whilst ALK transcripts have also been identified in the periphery.

    The physiological role of ALK has yet to be determined, although due to its expression profile it has been postulated to be involved in neuronal differentiation. ALK has two putative endogenous ligands, midkine (MK) and leiotrophin (PTN), which have both been implicated in neurite growth and have similar expression profiles to ALK. Ligand binding to ALK initiates homodimerization and autophosphorylation of the three tyrosine residues within the kinase domain, which results in tyrosine kinase activation. Downstream effectors of ALK tyrosine kinase activity have been shown to include the Ras-ERK, PI 3-K-Akt, JAK-STAT and NF-κB signaling pathways. In the absence of ligand binding ALK is inactive, with its expression promoting apoptosis. Conversely, when ALK is activated through either ligand binding or as part of an ALK fusion protein, apoptosis is decreased.

    The expression of many ALK fusion oncogenes have been implicated in the pathogenesis of many types of cancer. Examples include NPM-ALK, EML4-ALK and CLTLC-ALK which have been described in ALCL, non-small cell lung cancer (NSCLC) and diffuse large B cell lymphoma (DLBCL) respectively. ALK fusion proteins consist of a C-terminus composed of the intracellular tyrosine kinase domain of ALK and an N-terminus derived from the partner protein. The partner protein has been shown to induce constitutive kinase activation by mediating ALK dimerization. ALK is also involved in oncogenesis through overexpression and gain-of-function mutations. ALK is overexpressed in NSCLC, melanoma and certain types of breast cancer, amongst others, whilst point mutations in the ALK kinase domain have been implicated in neuroblastoma development.

    External sources of pharmacological information for ALK :

      Literature for ALK

      Cancer

      Cancer Research Product Guide

      A collection of over 750 products for cancer research, the guide includes research tools for the study of:

      • Cancer Metabolism
      • Epigenetics in Cancer
      • Receptor Signaling
      • Cell Cycle and DNA Damage Repair
      • Angiogenesis
      • Invasion and Metastasis
      Kinases

      Kinases Product Listing

      A collection of over 400 products for kinase research, the listing includes inhibitors of:

      • Receptor Tyrosine Kinases
      • Protein Kinases A, C, D and G
      • PI-3 Kinase, Akt and mTOR
      • MAPK Signaling
      • Receptor Serine/Threonine Kinases

      ALK Gene Data

      Gene Species Gene Symbol Gene Accession No. Protein Accession No.
      ALK Human ALK NM_004304 Q9UM73
      Mouse Alk NM_007439 NP_031465
      Rat Alk NM_001169101 NP_001162572