Fig. 5: Characteristics of the selected NR3 CG compounds.
a Recommended concentrations (Recom. conc.) refer to the recommended use of each compound in CG considering potency on the main NR3 target(s), activity type, NR off-targets and known off-targets outside the NR family. p(Potency) values refer to the pEC50 for agonists and to pIC50 for inverse agonists/antagonists reported in literature (n.a. no data available). Colors denote different NR3 subfamilies and match with the colors in Fig. 4a. Known off-targets of selected NR3 CG compounds are soluble epoxide hydrolase (sEH), phospholipase D1/2 (PLD1/2), aldehyde oxidase (AO), 17β-hydroxysteroid dehydrogenase 1/2 (17β-HSD1/2), nod-like receptor 3 (NLRP3), multi-catalytic protease (MCP), bile salt export pump (BSEP) and several cytochrome P450 (CYP) isoforms. b NR3 modulation profiles of the selected CG compounds. Compounds are labeled according to their mode of action (yellow - agonist, yellow with label M - modulator, grey - antagonist, grey with label D - degrader, orange - inverse agonist, green - inverse antagonist) and grouped by their NR3 subfamily main targets. The heatmap shows the potency expressed as pEC50 (red; agonists) or pIC50 (blue; antagonists and inverse agonists) reported in literature. For a few compounds, only single-point activity data but no EC50/IC50 have been reported (yellow; n.a.). c Correlations between the selected CG compounds and their NR3 targets. Multiple NR3 ligands with diverse activity profiles in the CG set enable deconvolution of phenotypic effects to NR3 receptors.
