Fig. 10: Validation of dual-agonism of VUFs at CXCR7.

a VUF10661 (green) and VUF11418 (pink) stimulate both CXCR3 and CXCR7 as measured in various assays. Data (mean ± SEM) represents either three (for βarr1/2 recruitment) or four (for cAMP response assay) independent biological replicates, performed in duplicate, and normalized with respect to signal observed at the lowest dose, treated either as 100% (for cAMP response), or 1 (βarr1/2 recruitment). VUF11207 (orange) has been previously characterized to be specific for CXCR7. b Heatmap showing βarr1 recruitment downstream to CXCR7 mutants following stimulation with VUF10661 (green) and VUF11418 (pink). Data (mean ± SEM) represents three independent experiments, performed in duplicate, and has been normalized with respect to the signal observed under unstimulated condition, treated as 1. c Mutating Y268A (blue) leads to a drastic reduction in βarr1 recruitment following stimulation with both VUFs, whereas mutating L128A (orange) ablates βarr1 recruitment upon stimulation with VUF10661 while eliciting only marginally reduced βarr1 recruitment following VUF11418 stimulation, as compared to wild-type CXCR7 (purple). Data (mean ± SEM) represents four independent experiments, performed in duplicate, and has been normalized with respect to the signal observed under unstimulated conditions, treated as 1. d Residues promoting allosteric communication in VUF10661-CXCR3 (green) exhibit similar rotameric shifts with respect to CCX662-CXCR7 (blue, PDB: 7SK9) and different orientations than those in VUF11418-CXCR3 (pink). Source data are provided as a Source Data file.