OXI-4503 (Combretastatin A1 Diphosphate): A Dual-Mechanism Vascular Disrupting Agent

I. Introduction

OXI-4503, also known as combretastatin A1 diphosphate (CA1P), is an investigational small molecule therapeutic agent derived from combretastatin A1, a natural product isolated from the South African bush willow tree, Combretum caffrum.[1] It is formulated as a solid diphosphate prodrug.[3] OXI-4503 has been primarily investigated for the treatment of various cancers and tumors, including solid tumors and hematologic malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).[5] The compound is characterized by a unique dual mechanism of action, functioning both as a potent vascular disrupting agent (VDA) that targets established tumor blood vessels and, following metabolic activation within the tumor microenvironment, as a direct cytotoxic agent against tumor cells.[1]

II. Chemical and Physical Properties

• Drug Name: OXI-4503 [User Query]
• Synonyms: Combretastatin A1 diphosphate (CA1P), Combretastatin A-1 phosphate, Combretastatin A-1 bis(phosphate) [2]
• Drug Type: Small Molecule [User Query]
• CAS Number: 288847-35-8 [4]
• DrugBank ID: DB05143 [5]
• Physical State: Solid [User Query]
• Chemical Formula (Parent): C18​H22​O12​P2​ [5]
• Molecular Weight (Parent): 492.3076 g/mol [5]
• Nature: OXI-4503 is a diphosphate prodrug of combretastatin A1 (CA1, OXi4500).[1] It requires in vivo dephosphorylation to release the active CA1 metabolite.[2] Salt forms such as dipotassium (DBSALT001872) and tetrasodium (3D67LX3H83) salts exist.[3]

III. Mechanism of Action

OXI-4503 exhibits a distinctive dual mechanism, combining vascular disruption with direct tumor cell cytotoxicity, setting it apart from many other vascular targeted therapies.[1]

Vascular Disrupting Agent (VDA) Activity