| Title | The protein tyrosine kinase inhibitors imatinib and nilotinib strongly inhibit several mammalian alpha-carbonic anhydrase isoforms. | | Author(s) | Parkkila S, Innocenti A, Kallio H, Hilvo M, Scozzafava A, Supuran CT | | Institution | Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland; School of Medicine, University of Tampere and Tampere University Hospital, Tampere, Finland. | | Source | Bioorg Med Chem Lett 2009 Jun 6. | | 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 (Glivec/Gleevec) and nilotinib (Tasigna) 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 K(I)s in the range of 4.1nM-20.2muM. CA I and CA II were the most potently inhibited isoforms (K(I)s of 4-32nM), whereas CA VA and VB showed the lowest affinity for these drugs (K(I)s of 5.4-20.2muM). In cancer cells, these inhibitors may interact with CAs in addition to the targets for which they were designed, the PTKs. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19527930 |
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