Multi-target kinase inhibitors

Kamath AV et al (2008) Preclinical pharmacokinetics and in vitro metabolism of dasatinib (BMS-354825) a potent oral multi-targeted kinase inhibitor against SRC and BCR-ABL. Cancer Chemother Pharmacol 61 365-376... 

Systems Biology Insights into Wrapping-Directed Design of Multi-target Kinase Inhibitors... 

Baratte S et al (2004) Quantitation of SU1 1248, an oral multi-target tyrosine kinase inhibitor, and its metabolite in monkey tissues by liquid chromatograph with tandem mass spectrometry following semi-automated liquid-liquid extraction. J Chromatogr A 1024 87-94... 

In the search for an optimal lead compound, not only activity on the desired target but also activity on other targets should be considered. Sometimes, multi-protein-targeting is desired, e.g., for multi-kinase inhibitors in the oncology field. However, also activity on side effect-related targets - so-called antitargets -is to be investigated. Compounds with no or very low affinity to proteins related to cardiovascular, cytotoxic, or metabolic effects are more likely to pass... 

Dinges, J., et al. l,4-dihydroindeno[l,2-c]pyrazoles with acetylenic side chains as novel and potent multi-targeted receptor tyrosine kinase inhibitors with low affinity for the hERG ion channel. J. Med. Chem. 2007, 50, 2011-2029. 

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