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 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.
Institut Curie/UMR9187-U1196, 91405 Orsay cedex, France; Univ Paris Sud, 91405 Orsay cedex, France.
Tom
T
Baladi
Institut Curie/UMR9187-U1196, 91405 Orsay cedex, France.
Valentina
V
Abet
Institut Curie/UMR9187-U1196, 91405 Orsay cedex, France; Univ Paris Sud, 91405 Orsay cedex, France. Electronic address: sandrine.piguel@u-psud.fr.
Sandrine
S
Piguel
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries; D020794:Receptor Protein-Tyrosine Kinases
Axl; Bioactive heterocycles; Mer; Nitrogen-containing small molecules; Tyro3; Tyrosine kinases inhibitors