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"Seriously Sweet": Acesulfame K Exhibits Selective Inhibition Using Alternative Binding Modes in Carbonic Anhydrase Isoforms.

J Med Chem 61 1176-1181 (2018)
Cited: 9 times
EuropePMC logo PMID: 29266943

Abstract

Human carbonic anhydrase IX (CA IX) is upregulated in neoplastic tissues; as such, it is studied as a drug target for anticancer chemotherapy. Inhibition of CA IX has been shown to be therapeutically favorable in terms of reducing tumor growth. Previously, saccharin, a commonly used artificial sweetener, has been observed to selectively inhibit CA IX over other CA isoforms. In this study, X-ray crystallography showed acesulfame potassium (Ace K) binding directly to the catalytic zinc in CA IX (mimic) and through a bridging water in CA II. This modulation in binding is reflected in the binding constants, with Ace K inhibiting CA IX but not other CA isoforms. Hence, this study establishes the potential of Ace K (an FDA approved food additive) as a lead compound in the design and development of CA IX specific inhibitors.

Reviews citing this publication (3)

  1. Experimental Carbonic Anhydrase Inhibitors for the Treatment of Hypoxic Tumors. Supuran CT. J Exp Pharmacol 12 603-617 (2020)
  2. Crystallography and Its Impact on Carbonic Anhydrase Research. Lomelino CL, Andring JT, McKenna R. Int J Med Chem 2018 9419521 (2018)
  3. Click chemistry approaches for developing carbonic anhydrase inhibitors and their applications. Angeli A, Supuran CT. J Enzyme Inhib Med Chem 38 2166503 (2023)

Articles citing this publication (6)