State-of-the-art of small molecule inhibitors of the TAM family: The point of view of the chemist

The TAM family of tyrosine kinases receptors (Tyro3, Axl and Mer) is implicated in cancer development, autoimmune reactions and viral infection and is therefore emerging as an effective and attractive therapeutic target. To date, only a few small molecules have been intentionally designed to block t...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2015-11, Vol.105, p.220-237
Main Authors: Baladi, Tom, Abet, Valentina, Piguel, Sandrine
Format: Article
Language:English
Subjects:
Animals
Axl
Bioactive heterocycles
Dose-Response Relationship, Drug
Humans
Mer
Models, Molecular
Molecular Structure
Nitrogen-containing small molecules
Protein Kinase Inhibitors - chemical synthesis
Protein Kinase Inhibitors - chemistry
Protein Kinase Inhibitors - pharmacology
Receptor Protein-Tyrosine Kinases - antagonists & inhibitors
Receptor Protein-Tyrosine Kinases - metabolism
Small Molecule Libraries - chemical synthesis
Small Molecule Libraries - chemistry
Small Molecule Libraries - pharmacology
Structure-Activity Relationship
Tyro3
Tyrosine kinases inhibitors
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Summary:The TAM family of tyrosine kinases receptors (Tyro3, Axl and Mer) is implicated in cancer development, autoimmune reactions and viral infection and is therefore emerging as an effective and attractive therapeutic target. To date, only a few small molecules have been intentionally designed to block the TAM kinases, while most of the inhibitors were developed for blocking different protein kinases and then identified through selectivity profile studies. This minireview will examine in terms of chemical structure the different compounds able to act on either one, two or three TAM kinases with details about structure–activity relationships, drug-metabolism and pharmacokinetics properties where they exist. [Display omitted] •Small molecules as inhibitors of Tyro3, Axl and Mer tyrosine kinases.•Crystal structures of Tyro3 and Mer are known.•SARs and DMPK properties of inhibitors targeting TAM kinases.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2015.10.003