Bioorganic & medicinal chemistry letters · 2009
The protein tyrosine kinase inhibitors imatinib and nilotinib strongly inhibit several mammalian alpha-carbonic anhydrase isoforms.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Parkkila Seppo, Innocenti Alessio, Kallio Heini, Hilvo Mika, Scozzafava Andrea, Supuran Claudiu T
Аннотация
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.