Structure-Activity Investigations and Optimisations of Non-metabolite Agonists for the Succinate Receptor 1

Research output: Contribution to journalJournal articleResearchpeer-review

The succinate receptor 1 (SUCNR1) is a receptor for the metabolite succinate, which functions as a metabolic stress signal in the liver, kidney, adipose tissue and the retina. However, potent non-metabolite tool compounds are needed to reveal the physiological role and pharmacological potential of SUCNR1. Recently, we published the discovery of a computationally receptor-structure derived non-metabolite SUCNR1 agonist series with high target selectivity. We here report our structure-activity exploration and optimisation that has resulted in the development of agonists with nanomolar potency and excellent solubility and stability properties in a number of in vitro assays. Ligand-guided receptor models with high discriminative power between binding of active and inactive compounds were developed for design of novel chemotypes.

Original languageEnglish
Article number10010
JournalScientific Reports
Issue number1
Pages (from-to)1-18
Publication statusPublished - 2018

Number of downloads are based on statistics from Google Scholar and

No data available

ID: 211856788