Anaplastic lymphoma kinase inhibitors as anticancer therapeutics: a patent review.
BACKGROUND
Anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase from the insulin receptor superfamily, is implicated in the oncogenesis of numerous cancers including anaplastic large-cell lymphoma, non-small-cell lung cancer, diffuse large B-cell lymphoma, inflammatory myofibroblastic tumors, glioblastoma, as well as neuroblastoma. The root cause for these specific cancers has been identified as aberrant ALK kinase activity, which has been shown to be associated with specific gene translocations, single-point mutations, gene amplification and/or overexpression. The direct inhibition of ALK with small-molecule inhibitors represents a viable therapeutic intervention that has achieved clinical proof of concept.


METHODS
Small-molecule ALK inhibitors covered in the patent literature from 2010 to September 2013 are described. Relevant peer-reviewed journal articles that describe discovery and development of the above-identified ALK inhibitors are also discussed. Keyword-based (e.g., ALK, anaplastic lymphoma kinase) literature searches were conducted in Scifinder®.


CONCLUSIONS
Novel ALK inhibitors continued to be discovered at a fast pace over the covered period, with many distinct chemotypes emerging. Crizotinib received FDA approval in 2011, and six additional ALK inhibitors have entered clinical trials. The focus of ALK research appears to have shifted toward inhibitors that display activity against resistant mutants unearthed in clinical studies with crizotinib.
Teva Branded Pharmaceutical Products R&D, Inc. , 145 Brandywine Parkway, West Chester, PA 19380 , USA +1 610 738 6168 ; Eugen.Mesaros@tevapharm.com.
Eugen F
EF
Mesaros
Gregory R
GR
Ott
Bruce D
BD
Dorsey
D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077547:Crizotinib; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D010330:Patents as Topic; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases