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Studies in animal models of osteoarthritis as predictors of a structure-modifying effect of diacerhein in humans with osteoarthritis

机译:骨关节炎动物模型中透皮素的结构修饰作用预测因子的研究

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摘要

In addressing the use of animal models of osteoarthritis (OA) for predicting a structure-modifying effect of the anthraquinone derivative, diacerhein (DAR) (Fig. 1), in humans with OA, it is worth considering at the outset the context for the use of animal models, in general, as predictors of drug effects in humans with OA. In this vein, the excellent chapter by Doherty et al. [6] on the limitations of animal models in OA research provides excellent background. Paradigms of drug development based on animal models rely chiefly on demonstration of therapeutic activity in an animal model of the human disease to justify moving on to evaluation of the compound in man. In contrast, mechanism-based paradigms involve identification of a specific target (e.g., cytokine, enzyme, receptor) that is presumed to be important in the human disease and the selection of compounds that have appropriate activities against the target in vitro in assays utilizing appropriate human reagents, ensuring that the compound possesses the necessary pharmacodynamic properties. Promising compounds may then be evaluated in humans without a requirement for demonstration of therapeutic efficacy in an animal model of the disease.
机译:在探讨使用骨关节炎(OA)的动物模型预测蒽醌衍生物diahehehein(DAR)(图1)在患有OA的人中的结构修饰作用时,值得一开始考虑一下通常将动物模型用作OA人体药物作用的预测指标。在这种情况下,Doherty等人撰写的精彩文章。 [6]关于动物模型的局限性在OA研究中提供了极好的背景。基于动物模型的药物开发范例主要依赖于人类疾病动物模型中治疗活性的证明,以证明继续评估人体内化合物的合理性。相反,基于机制的范例涉及鉴定对人类疾病重要的特定靶标(例如,细胞因子,酶,受体),以及在使用适当试剂的试验中选择对靶标具有适当活性的化合物人类试剂,确保该化合物具有必要的药效特性。然后可以在人中评估有希望的化合物,而无需在该疾病的动物模型中证明其治疗功效。

著录项

  • 来源
    《Biorheology》 |2006年第4期|p.589-594|共6页
  • 作者

    Kenneth D. Brandt;

  • 作者单位

    Indiana University School of Medicine, Division of Rheumatology, 1110 West Michigan Street, Room LO 545, Indianapolis, IN 46202, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物科学;
  • 关键词

  • 入库时间 2022-08-18 01:12:01

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