Recent advances in the development of multi-kinase inhibitors.
During the last two decades, protein kinases have emerged as a major target for cancer therapy and a large number of selective kinase inhibitors have been developed as potential anticancer drugs. To avoid unpredictable toxic effects, researchers usually aim at designing highly selective inhibitors. But since the formation and progression of a tumor has to be considered as a multifactorial process, which is dependent on different signalling pathways, it seems reasonable to establish anticancer therapies that target several kinases associated with tumor growth. In general, this can be achieved by two different strategies, either by concomitantly using a combination of a set of selective kinase inhibitors or by administering a single agent, which simultaneously inhibits several kinases, a so called multi-kinase inhibitor. In this review, benefits and obstacles of both strategies are discussed. An overview over recently approved and newly upcoming multi-kinase inhibitors is given.
Krug
Martin
M
Martin Luther University Halle-Wittenberg, Institute of Pharmacy, Wolfgang-Langenbeck-Strasse 4, 06120 Halle (Saale), Germany.
Hilgeroth
Andreas
A
D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000494:pharmacology; D002224:Carbanilides / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007191:Indazoles / Q000138:chemical synthesis / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology; D010793:Phthalazines / Q000138:chemical synthesis / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis / Q000494:pharmacology
D001549:Benzamides; D002224:Carbanilides; D007191:Indazoles; D007211:Indoles; D010793:Phthalazines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011799:Quinazolines; D011494:Protein Kinases