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

Seppo Parkkila, Alessio Innocenti, Heini Kallio, Mika Hilvo, Andrea Scozzafava, Claudiu T. Supuran (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

54 Citations (Scopus)

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 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.
Original languageEnglish
Pages (from-to)4102-4106
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number15
DOIs
Publication statusPublished - 2009
MoE publication typeA1 Journal article-refereed

Keywords

  • Imatinib
  • Nilotinib
  • Carbonic anhydrase
  • Isoforms I-XV
  • Antitumor drug

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