Peroxisome proliferator-activated receptor translational research and clinical experience
Peroxisome proliferator-activated receptor translational research and clinical experience
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DOI：
10.3945/ajcn.2009.28449d
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发表时间：
2010-01-01
影响因子：
7.1
通讯作者：
Cheatham, Wayman Wendell
中科院分区：
文献类型：
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作者：
Cheatham, Wayman Wendell
自 20 世纪 70 年代初以来，药物生物化学家一直在寻求利用在研究纤维酸衍生物的功能和作用模式基础时发现的科学发现。在 20 世纪 70 年代初期，人们对过氧化物酶体增殖物激活受体 (PPAR) 知之甚少，甚至在概念上也是如此。然而，从那时起，医学科学中生物活性小分子的发展导致了插入 PPAR 结合结构域的工具的开发，这导致了对结合构型的数千种可能的生物效应的认识。在糖尿病护理领域，基于这些发现和发展的第一个上市药物于 1996 年推出。它很有效，而且效果很好。然而，使用这种早期形式的噻唑烷二酮有时（尽管很少见）会导致暴发性肝衰竭，最终该药物被从市场上撤下。随后又开发了噻唑烷二酮类药物，其中有2种比较成功。然而，他们也并非没有问题。本文描述了这些药物的开发历史，确定了它们所具有的宝贵属性，并给出了为什么仍在寻求“更安全”的 PPAR 激动剂的明确理由。 Am J Clin Nutr 2010；91（增刊）：262S-6S。
Since the early 1970s, pharmaceutical biochemists have sought to exploit the scientific findings that were uncovered when they studied the basis for the function and mode of action of fibric acid derivatives. In the early 1970s, little was known of peroxisome proliferator-activated receptors (PPARs), even in concept. Since then, however, the development of bioactive small molecules in medicinal science has resulted in tools developed to be inserted into the PPAR-binding domain, which has resulted in the recognition of literally thousands of possible biological effects of binding configurations. In diabetes care, the first of the marketed agents from these discoveries and developments was introduced in 1996. It was potent and did its job well. However, the use of this early form of thiazolidinedione sometimes, although rarely, led to fulminant liver failure, and ultimately the drug was removed from the market. Subsequent thiazolidinediones have been developed, and 2 have been relatively successful. However, they are not without their problems. This article describes the history of the development of these drugs, identifies the valuable attributes that they possess, and gives a clear rationale as to why a quest for a "safer" PPAR agonist is still being sought. Am J Clin Nutr 2010;91(suppl):262S-6S.