碘甲状腺素脱碘酶构成一组三种富含硒的酶，调节甲状腺激素（T4和T3）的胞内代谢以及对多种生理过程，包括能量代谢、发育和细胞分化产生影响。D1、D2和D3的甲状腺素脱碘酶是TH轴中的敏感的速率限制性组成部分，在生理条件或疾病中迅速控制TH的作用。值得注意的是，一些人类病理症状特征是甲状腺素脱碘酶失调（例如，炎症、骨质疏松、代谢综合症、肌肉萎缩和癌症）。因此，这些酶是识别和开发具有调节活性的药物化合物的黄金靶点。然而，迄今为止，甲状腺素脱碘酶抑制剂的资料有限，少数有效的化合物缺乏选择性。在这里，我们描述了头孢噻肟作为一种新的D2特异性抑制剂。在体内和体外环境中，头孢噻肟作为D2活性的选择性抑制剂，而不影响D1和D3的酶活性。通过抑制目标组织中的TH活化，头孢噻肟改变下丘脑-垂体轴的敏感性并干扰TH水平的中央调节，因此有资格成为患有甲状腺功能亢进的病人的潜在新调节剂，这种病状全球有数千名患者。版权所有 © 2023 作者。由Elsevier Ltd.发布。保留所有权利。

The iodothyronine deiodinases constitute a family of three selenoenzymes regulating the intracellular metabolism of Thyroid Hormones (THs, T4 and T3) and impacting on several physiological processes, including energy metabolism, development and cell differentiation. The type 1, 2 and 3 deiodinases (D1, D2, and D3), are sensitive, rate-limiting components within the TH axis, and rapidly control TH action in physiological conditions or disease. Notably, several human pathologies are characterized by deiodinases deregulation (e.g., inflammation, osteoporosis, metabolic syndrome, muscle wasting and cancer). Consequently, these enzymes are golden targets for the identification and development of pharmacological compounds endowed with modulatory activities. However, until now, the portfolio of inhibitors for deiodinases is limited and the few active compounds lack selectivity. Here, we describe the cephalosporin Cefuroxime as a novel D2 specific inhibitor. In both in vivo and in vitro settings, Cefuroxime acts as a selective inhibitor of D2 activity, without altering the enzymatic activity of D1 and D3. By inhibiting TH activation in target tissues, Cefuroxime alters the sensitivity of the hypothalamus-pituitary axis and interferes with the central regulation of THs levels, and is thus eligible as a potential new regulator of hyperthyroid pathologies, which affect thousands of patients worldwide.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.