【1-3】Synthesis and biological evaluation of novel bivalent GPCR ligands


报告题目:Synthesis and biological evaluation of novel bivalent GPCR ligands

报 告 人:钱明成 博士(根特大学-比利时)





Dr. Mingcheng Qian received his PhD degree in Medicinal Chemistry at Ghent University (Belgium) in November 2018. His PhD work was mainly focused on synthesis and biological evaluation of novel bivalent G protein-coupled receptors (GPCRs) ligands. During his PhD period, he found two new pairs of GPCR heterodimers, which could be the new potential drug targets for the treatment of pain and/or Parkinson’s disease. From January 2018, Dr. Qian has been in the same research group as a research assistant and working on the synthesis and evaluation of bivalent ligands for yet unexplored GPCR heterodimers, involving dopamine D2 and muscarinic M1 receptors, both key targets for the treatment of Parkinson's disease.


G protein-coupled receptors (GPCRs) represent the largest group of cell membrane receptors. More than 30% of today’s clinically used drugs act directly or indirectly on GPCRs. For a long time, GPCRs have been considered to exist and function as monomers within the plasma membrane. However, in the past decades an increasing number of studies revealed that GPCRs are capable of forming dimers or even higher-ordered oligomers, which may modulate receptor function. Nowadays, heterobivalent ligands have emerged as valuable tools to demonstrate the existence of GPCR heteromers without the need for receptor modification. Heterobivalent ligands with a spacer of optimal length are envisaged to exhibit a potency that is different from that derived from its two monovalent pharmacophores. Compounds able to modulate two GPCR dimers may eventually also evolve to useful pharmacological agents that target selected heteromeric subtypes, thereby potentially increasing selectivity.