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Issue 66, 2012
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Polypharmacology of sulfonamides: pazopanib, a multitargeted receptor tyrosine kinase inhibitor in clinical use, potently inhibits several mammalian carbonic anhydrases

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Abstract

Pazopanib, a new, multi-targeted tyrosine kinase inhibitor (TKI) used clinically for the treatment of several types of tumors, incorporates a primary sulfonamide moiety normally associated with the inhibition of the metallo enzyme carbonic anhydrase (CA, EC 4.2.1.1). Here we show that pazopanib and related sulfonamides such as indisulam, acetazolamide or ureido-substituted peptidomimetic benzenesulfonamides are low nanomolar inhibitors of many of the fifteen human isoforms hCA I–XIV. These data indicate that in addition to the TK inhibitory action, pazopanib may exert antitumor/antimetastatic effects also due to the potent inhibition of the tumor-associated, hypoxia-inducible enzymes CA IX and XII.

Graphical abstract: Polypharmacology of sulfonamides: pazopanib, a multitargeted receptor tyrosine kinase inhibitor in clinical use, potently inhibits several mammalian carbonic anhydrases

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Publication details

The article was received on 11 May 2012, accepted on 10 Jun 2012 and first published on 12 Jun 2012


Article type: Communication
DOI: 10.1039/C2CC33415A
Chem. Commun., 2012,48, 8177-8179

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    Polypharmacology of sulfonamides: pazopanib, a multitargeted receptor tyrosine kinase inhibitor in clinical use, potently inhibits several mammalian carbonic anhydrases

    J. Winum, A. Maresca, F. Carta, A. Scozzafava and C. T. Supuran, Chem. Commun., 2012, 48, 8177
    DOI: 10.1039/C2CC33415A

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