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.

中文翻译：

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“非常甜”：乙酰磺胺酸钾在碳酸酐酶同工型中使用其他结合模式表现出选择性抑制作用

肿瘤组织中人碳酸酐酶IX（CA IX）上调；因此，已将其作为抗癌化学疗法的药物靶标进行了研究。在减少肿瘤生长方面，已经显示出对CA IX的抑制在治疗上是有利的。以前，糖精（一种常用的人造甜味剂）已被观察到比其他CA异构体有选择性地抑制CA IX。在这项研究中，X射线晶体学显示乙酰磺胺酸钾（Ace K）直接与CA IX中的催化锌结合（模拟），并通过CA II中的桥联水结合。结合中的这种调节反映在结合常数中，其中Ace K抑制CA IX，但不抑制其他CA同种型。因此，这项研究确定了Ace K（一种FDA批准的食品添加剂）在设计和开发CA IX特异性抑制剂中作为先导化合物的潜力。