oxi-4503

OXI-4503 is an investigational small molecule vascular disrupting agent (VDA) derived from the natural product combretastatin A1. It is a diphosphate prodrug that, upon administration, is dephosphorylated in vivo to release the active metabolite. OXI-4503 exerts a dual mechanism of action: it disrupts tumor vasculature by binding reversibly to tubulin at the colchicine binding site in bone marrow endothelial cells, leading to changes in cell shape and downregulation of intercellular adhesion molecules. This process releases quiescent tumor cells and sensitizes them to chemotherapy. Additionally, within the tumor microenvironment, oxidative enzymes convert OXI-4503 into an orthoquinone species with direct cytotoxic effects on tumor cells. The drug has demonstrated single-agent activity against various xenograft models and shows synergistic or additive effects when combined with chemotherapy or targeted therapies. It has been primarily investigated for hematologic malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), as well as advanced solid tumors[1][2][4][5][7][8].

Brand names

OXi4503OXi-4503OXi 4503

Other names

combretastatin A1 diphosphateCA1PCA-1PCA 1Pcombretastatin A-1 bis(phosphate)combretastatin A1 phosphate