The M.S. University of Baroda, Faculty of Technology & Engineering, Department of Pharmacy, Kalabhavan, Vadodara, 390 001, India.
Expert Opin Ther Pat. 2010 Jan;20(1):31-57. doi: 10.1517/13543770903465157.
TNF-alpha converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-alpha from membrane bound TNF-alpha precursor protein. TNF-alpha is believed to play pathophysiological roles in inflammation, anorexia, cachexia, septic shock, viral replication and so on. TNF-alpha is a key player in inflammation and joint damage in rheumatoid arthritis. While a variety of TACE inhibitors have been reported in the literature, a vast majority of these compounds are peptidic and peptide-like compounds that are expected to have bioavailability and pharmacokinetic problems, common to such compounds, limiting their clinical effectiveness. Low molecular mass, long acting, orally bioavailable inhibitors of TACE are, therefore, highly desirable for the treatment of potential chronic diseases mentioned above. A review of patented compounds as TACE inhibitors in drug discovery is given. A selection of interesting patents recorded from 2001 to 2009 is presented. Various novel TACE inhibitors developed by different companies have been discussed.
肿瘤坏死因子-α 转换酶（TACE）是一种促炎细胞因子，能够催化膜结合型 TNF-α 前体蛋白转化为 TNF-α。TNF-α 被认为在炎症、厌食、恶病质、感染性休克、病毒复制等方面发挥着病理生理学作用。TNF-α 是类风湿关节炎中炎症和关节损伤的关键因素。尽管文献中已经报道了多种 TACE 抑制剂，但这些化合物绝大多数是肽类和类肽化合物，预计会存在生物利用度和药代动力学方面的问题，这些问题在这类化合物中很常见，限制了它们的临床效果。因此，对于上述潜在的慢性疾病的治疗，小分子、长效、口服生物利用度的 TACE 抑制剂是非常需要的。本文对药物研发中作为 TACE 抑制剂的专利化合物进行了综述。介绍了 2001 年至 2009 年记录的一些有趣的专利。讨论了不同公司开发的各种新型 TACE 抑制剂。
