TAT-cyclo-CLLFVY is a selective HIF-1 dimerization inhibitor. TAT-cyclo-CLLFVY blocks protein-protein interaction of recombinant HIF-1α, but not HIF-2α, with HIF-1β (IC50=1.3 μM). TAT-cyclo-CLLFVY inhibits hypoxia-induced HIF-1 activity and decreases VEGF and CAIX expression in osteosarcoma and breast cancer cells in vitro. TAT-cyclo-CLLFVY also reduces the tubularization of hypoxic HUVECs.