IT1t

IT1t is a chemokine (C-X-C motif) receptor 4 (CXCR4) antagonist (IC₅₀s = 8 and 11 nM for the human and rat receptors, respectively).¹ It is selective for CXCR4 over human ether-a-go-go-related gene potassium channels (hERG/K_v11.1; IC₅₀ = 13,240 nM). IT1t inhibits calcium mobilization induced by chemokine (C-X-C-motif) ligand 12 (CXCL12) in CEM cells (IC₅₀ = 1.1 nM) and decreases CXCL12-induced migration of Jurkat cells (IC₅₀ = 79.1 nM).^1,2 It inhibits replication of the HIV-1 strain NL4-3 in MT-4 cells and isolated human peripheral blood mononuclear cells (PBMCs) stimulated with phytohemagglutinin (PHA; IC₅₀s = 14.2 and 19 nM, respectively).² IT1t (20 ?M) reduces tumor growth in an MDA-MB-231-B zebrafish xenograft model.³

1.Thoma, G., Streiff, M.B., Kovarik, J., et al.Orally bioavailable isothioureas block function of the chemokine receptor CXCR4 in vitro and in vivoJ. Med. Chem.51(24)7915-7920(2008) 2.Van Hout, A., D'huys, T., Oeyen, M., et al.Comparison of cell-based assays for the identification and evauation of competitive CXCR4 inhibitorsPLoS One12(4)e0176057(2017) 3.Tulotta, C., Stefanescu, C., Beletkaia, E., et al.Inhibition of signaling between human CXCR4 and zebrafish ligands by the small molecule IT1t impairs the formation of triple-negative breast cancer early metastases in a zebrafish xenograft modelDis. Model Mech.9(2)141-153(2016)