Origin Pharmaceuticals, Inc., Wayne, PA 19087, USA.
Expert Opin Ther Pat. 2010 Aug;20(8):1047-57. doi: 10.1517/13543776.2010.496777.
The farnesoid X receptor (FXR) is a key regulator of cholesterol homeostasis, triglyceride synthesis and lipogenesis. Given some patients' inability to tolerate existing medications, such as the statins, for cholesterol reduction, there is a pressing need for additional medicines to treat dyslipidemia. FXR agonists have emerged in discovery and preclinical efforts to show great potential for the treatment of these and other life-impairing and life-threatening conditions.
Recent advances in the search for novel FXR modulators are reviewed, with a particular focus on patent applications and peer-reviewed publications disclosed in the past 5 years.
A total of 72 patent applications and peer-reviewed articles, containing 16 generic structure classes with nearly 5000 novel synthesized structures are reviewed. Where possible, the structure-activity relationship of these structure classes is surveyed, new insights into in vitro and in vivo efficacy of FXR agonists are disclosed, and potential new and promising therapeutic applications are revealed.
FXR agonists have proven their efficacy and safety in primates and have significant potential as therapeutic agents for the treatment of dyslipidemia and potentially an array of other disease areas.
法尼醇 X 受体 (FXR) 是胆固醇稳态、甘油三酯合成和脂肪生成的关键调节剂。鉴于一些患者无法耐受现有的降胆固醇药物，如他汀类药物，因此迫切需要其他药物来治疗血脂异常。FXR 激动剂在发现和临床前研究中已经出现，它们具有治疗这些和其他危及生命的疾病的巨大潜力。
回顾了寻找新型 FXR 调节剂的最新进展，特别关注过去 5 年披露的专利申请和同行评议出版物。
共审查了 72 项专利申请和同行评议文章，其中包含 16 个通用结构类别，近 5000 个新合成的结构。在可能的情况下，对这些结构类别的构效关系进行了调查，揭示了 FXR 激动剂在体外和体内疗效的新见解，并揭示了其可能的新的有前途的治疗应用。
FXR 激动剂已在灵长类动物中证明了其疗效和安全性，它们具有作为治疗血脂异常和潜在一系列其他疾病领域的治疗剂的巨大潜力。
