Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10596309 | Bioorganic & Medicinal Chemistry Letters | 2009 | 5 Pages |
Abstract
The protein tyrosine kinases (PTKs) are essential enzymes in cellular signaling processes that regulate cell growth, differentiation, migration and metabolism. Their inhibition was recently shown to constitute a new modality for treating cancers. Two clinically used PTK inhibitors (PTKIs), imatinib (Glivecâ¢/Gleevecâ¢) and nilotinib (Tasignaâ¢) were investigated for their effects on the zinc enzymes carbonic anhydrases (CAs, EC 4.2.1.1). The two PTKIs inhibited all 13 catalytically active mammalian isoforms CA I-XV with KIs in the range of 4.1 nM-20.2 μM. CA I and CA II were the most potently inhibited isoforms (KIs of 4-32 nM), whereas CA VA and VB showed the lowest affinity for these drugs (KIs of 5.4-20.2 μM). In cancer cells, these inhibitors may interact with CAs in addition to the targets for which they were designed, the PTKs.
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Authors
Seppo Parkkila, Alessio Innocenti, Heini Kallio, Mika Hilvo, Andrea Scozzafava, Claudiu T. Supuran,