ATI-2341 (trifluoroacetate salt)

ATI-2341 is a pepducin Gα_i-signaling biased agonist of chemokine (C-X-C motif) receptor 4 (CXCR4).¹ It induces dissociation of Gα_i and Gγ₂, indicating activation of Gα_i-signaling, with an EC₅₀ value of 0.21 µM in a bioluminescence resonance energy transfer (BRET) assay using HEK293T cells expressing CXCR4. ATI-2341 is selective for Gα_i over Gα₁₃ (EC₅₀s = 0.53 and >1 µM, respectively, in BRET engagement assays) and is biased for Gα_i engagement over β-arrestin-2, G protein-coupled receptor kinase 2 (GRK2), or GRK3 recruitment, exhibiting bias factor values of 24, 24.9, and 30, respectively. It induces chemotaxis of CCRF-CEM T cells, which endogenously express CXCR4, in a concentration-dependent manner. ATI-2341 (0.45 µmol/kg) increases peritoneal lavage fluid infiltration of polymorphonuclear leukocytes (PMNs) in mice.²

1.Quoyer, J., Janz, J.M., Luo, J., et al.Pepducin targeting the C-X-C chemokine receptor type 4 acts as a biased agonist favoring activation of the inhibitory G proteinProc. Natl. Acad. Sci. USA110(52)5088-5097(2013) 2.Tchernychev, B., Ren, Y., Sachdev, P., et al.Discovery of a CXCR4 agonist pepducin that mobilizes bone marrow hematopoietic cellsProc. Natl. Acad. Sci. USA107(51)22255-22259(2010)