Fig. 11.
Developing affinity MS approaches for GPCR ligand screening. a Experimental workflow of membrane-based affinity MS. b Membrane-based affinity MS screening of 4333 compounds split into 9 cocktails against GLP-1R. Initial hits are indicated by red dots, while gray dots represent negatives. c Binding of one new ligand to 5-HT2C (upper) and four new ligands to GLP-1R (lower) were validated by a radioligand-binding assay. d Experimental workflow of affinity MS-based screening of natural herb extracts. e Initial hits from screening fractionated herbal extracts toward 5-HT2C. Aporphines are annotated with larger pink dots. BI binding index. f Structural validation of 1857 by MSMS analysis. g 1857 displayed selective agonism at 5-HT2C. Source: adapted from Qin et al.266 and Zhang et al.282