A new clinically used cancer drug thought to work by inhibiting kinase enzymes also strongly inhibits carbonic anhydrase (CA) enzymes, reveal scientists in Italy.
Scientists did not evaluate the CA inhibition activity of pazopanib before its approval for the treatment of a variety of different cancers, including lung, breast and ovarian cancers. But Claudiu Supuran and colleagues recognised part of the drug’s structure – a primary sulfonamide moiety – is often found in drugs that can inhibit CAs. So they tested pazopanib along with some other related structures and found that the drug did indeed inhibit CAs. They estimate that a significant proportion of the drug’s therapeutic effect on hypoxic tumors is due to its strong CA inhibitory properties.
Link to journal article
Polypharmacology of sulfonamides: Pazopanib, a multitargeted receptor tyrosine kinase inhibitor in clinical use, potently inhibits several mammalian carbonic anhydrases
J-Y Winum et al
Chem. Commun., 2012, DOI: 10.1039/c2cc33415a