Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 19 (15), 4102-6

The Protein Tyrosine Kinase Inhibitors Imatinib and Nilotinib Strongly Inhibit Several Mammalian Alpha-Carbonic Anhydrase Isoforms

Affiliations

The Protein Tyrosine Kinase Inhibitors Imatinib and Nilotinib Strongly Inhibit Several Mammalian Alpha-Carbonic Anhydrase Isoforms

Seppo Parkkila et al. Bioorg Med Chem Lett.

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-20.2microM. 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 5.4-20.2microM). In cancer cells, these inhibitors may interact with CAs in addition to the targets for which they were designed, the PTKs.

Similar articles

See all similar articles

Cited by 12 PubMed Central articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources

Feedback