Recent Updates on Structural Aspects of ALK Inhibitors as an Anticancer Agent

Author(s):

Md Shahid Ayaz, Ritu Bhupal, Priyanka Sharma, Adarsh Sahu, Parwati Singh, Ghanshyam Das Gupta and Vivek Asati*   Pages 900 - 921 ( 22 )

Abstract:

Presently, several protein kinases have been discovered with the aim to treat various cancers. Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that plays a role in the pathogenesis of a wide variety of human cancers known as ALCLs, NSCLC, ovarian cancer, breast cancer, colorectal cancer, neuroblastoma, etc. The fulllength ALK receptor is a classical receptor tyrosine kinase composed of an amino-terminal extracellular domain and an intracellular tyrosine kinase domain. Crizotinib is a strong oral small-molecule first tyrosine kinase inhibitor of ALK to be used in the treatment of ALK-dependent NSCLC. Due to the drug resistance of first generation ALK inhibitors, researchers are trying to design and synthesize novel ALK inhibitors with various heterocyclic rings in which 2,4- diarylaminopyrimidine derivatives with a specific N-(3-pyridinylmethyl)urea moiety, 2-amino-4-(1-piperidine) pyridine derivatives, 7-azaindole and carboxamide derivatives and some others produced potential compounds. To overcome drug resistance, to get better affinity and to reduce drug toxicity, there is an urgent need for novel ALK inhibitors. The present review describes the ALK signaling, their inhibitors and related structure activity relationships for the development of potential ALK inhibitors.

Keywords:

Anaplastic lymphoma kinase, tyrosine kinase, mesenchymal-epithelial transition, anaplastic large-cell lymphoma, leukocyte tyrosine kinase, non small cell lung cancer.

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