School of Biology, Department Biochemistry and Molecular Biomedicine, University of Barcelona, 08028 Barcelona, Spain.
RG Neuroplasticity, Leibniz Institute for Neurobiology, Brenneckestr. 6., 39118 Magdeburg, Germany.
Molecules. 2020 Oct 30;25(21):5060. doi: 10.3390/molecules25215060.
G protein-coupled receptors (GPCRs), which constitute the most populous family of the human proteome, are the target of 35-45% of approved therapeutic drugs. This review focuses on natural products (excluding peptides) that target GPCRs. Natural compounds identified so far as agonists, antagonists or allosteric modulators of GPCRs have been found in all groups of existing living beings according to Whittaker's Five Kingdom Classification, i.e., bacteria (monera), fungi, protoctists, plants and animals. Terpenoids, alkaloids and flavonoids are the most common chemical structures that target GPCRs whose endogenous ligands range from lipids to epinephrine, from molecules that activate taste receptors to molecules that activate smell receptors. Virtually all of the compounds whose formula is displayed in this review are pharmacophores with potential for drug discovery; furthermore, they are expected to help expand the number of GPCRs that can be considered as therapeutic targets.
G 蛋白偶联受体（GPCRs）是人类蛋白质组中最大的家族，它们是 35-45%已批准治疗药物的靶点。本综述专注于靶向 GPCR 的天然产物（不包括肽）。根据惠塔克的五界分类法，目前已在所有现有生物群中发现了作为 GPCR 激动剂、拮抗剂或别构调节剂的天然化合物，包括细菌（原核生物）、真菌、原生生物、植物和动物。萜类、生物碱和类黄酮是靶向 GPCR 的最常见化学结构，其内源性配体范围从脂质到肾上腺素，从激活味觉受体的分子到激活嗅觉受体的分子。在本综述中展示其分子式的几乎所有化合物都是具有药物发现潜力的药效团；此外，它们有望帮助扩大可被视为治疗靶点的 GPCR 数量。
