Abstract：
Peroxisome proliferator-activated receptors (PPARs) have been exploited as drug targets for combating multiple diseases. Several activators with different selectivity for the PPAR α, γ, and δ subtypes have been introduced into the market or have reached advanced clinical trials. Binding assays are of utmost importance for the discovery and profiling of such PPAR ligands. Binding assays are often based on radioligands, in particular, tritiated molecules are applied. We developed synthetic procedures for tritiating various PPAR agonists and applied these radioligands for setting up a scintillation proximity assay (SPA) for PPAR α, γ, and δ. These SPAs allow to assess the binding affinities of PPAR α, γ, and δ ligands, along with their respective subtype selectivity profiles. Therefore, SPA is an important tool for hit discovery and lead optimization campaigns aimed at identifying next-generation PPAR ligands.
摘要：
过氧化物酶体增殖物激活受体(PPAR)已被用作对抗多种疾病的药物靶标。几种对PPARα具有不同选择性的活化剂，γ,和δ亚型已被引入市场或已达到先进的临床试验。结合测定对于此类PPAR配体的发现和谱分析是最重要的。结合测定通常基于放射性配体，特别是,应用氚化的分子。我们开发了用于tri化各种PPAR激动剂的合成程序，并将这些放射性配体用于建立PPARα的闪烁接近测定（SPA），γ,和δ。这些SPA允许评估PPARα的结合亲和力，γ,和δ配体，以及它们各自的亚型选择性概况。因此,SPA是命中发现和铅优化活动的重要工具，旨在识别下一代PPAR配体。
