The protein tyrosine kinase inhibitors imatinib and nilotinib strongly inhibit several mammalian alpha-carbonic anhydrase isoforms.
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Parkkila S, Innocenti A, Kallio H, Hilvo M, Scozzafava A, Supuran CT
The protein tyrosine kinase inhibitors imatinib and nilotinib strongly inhibit several mammalian alpha-carbonic anhydrase isoforms.
Bioorg Med Chem Lett. 2009 Aug 1;19(15):4102-6. doi: 10.1016/j.bmcl.2009.06.002. Epub 2009 Jun 6.
- PubMed ID
- 19527930 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Acetazolamide Carbonic anhydrase 1 Ki (nM) 250 N/A N/A Details Acetazolamide Carbonic anhydrase 12 Ki (nM) 5.7 N/A N/A Details Acetazolamide Carbonic anhydrase 14 Ki (nM) 41 N/A N/A Details Acetazolamide Carbonic anhydrase 2 Ki (nM) 12 N/A N/A Details Acetazolamide Carbonic anhydrase 3 Ki (nM) 200000 N/A N/A Details Acetazolamide Carbonic anhydrase 4 Ki (nM) 74 N/A N/A Details Acetazolamide Carbonic anhydrase 7 Ki (nM) 2.5 N/A N/A Details