Although wild type CXCL12, CXCL121 and CXCL122 showed comparable CXCR4 and ACKR3 activities in Presto-Tango β-arrestin recruitment assays, distinct pharmacokinetic and pharmacodynamic properties have been observed in various other signaling and cell function assays in vitro, in an isolated rat heart ischemia–reperfusion injury model and in a melanoma lung metastasis model21,32,33. This evidence concerns the gene CXCR4 and melanoma.