The protein tyrosine kinase inhibitors imatinib and nilotinib strongly inhibit several mammalian α-carbonic anhydrase isoforms

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 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.