OXI-4503
- Generic Name
- OXI-4503
- Drug Type
- Small Molecule
- Chemical Formula
- C18H22O12P2
- CAS Number
- 288847-35-8
- Unique Ingredient Identifier
- JH6Z94GLUD
Overview
OXI-4503 is investigated in clinical trials for treating cancer/tumors. OXI-4503 is a solid. OXI-4503 blocks and destroys tumor vasculature, resulting in extensive tumor cell death and necrosis. OXI-4503 (combretastatin A1 di-phosphate / CA1P) is a unique and highly potent, dual-mechanism vascular disrupting agent (VDA). In addition, however, preclinical data demonstrates that OXI-4503 is metabolized by oxidative enzymes (e.g., tyrosinase and peroxidases), which are elevated in many solid tumors and tumor infiltrates, to an orthoquinone chemical species that has direct cytotoxic effects on tumor cells. Preclinical studies have demonstrated that OXI-4503 has (i) single-agent activity against a range of xenograft tumor models; and (ii) synergistic or additive effects when incorporated in various combination regimens with chemotherapy, molecularly-targeted therapies (including tumor-angiogenesis inhibitors), and radiation therapy.
Background
OXI-4503 is investigated in clinical trials for treating cancer/tumors. OXI-4503 is a solid. OXI-4503 blocks and destroys tumor vasculature, resulting in extensive tumor cell death and necrosis. OXI-4503 (combretastatin A1 di-phosphate / CA1P) is a unique and highly potent, dual-mechanism vascular disrupting agent (VDA). In addition, however, preclinical data demonstrates that OXI-4503 is metabolized by oxidative enzymes (e.g., tyrosinase and peroxidases), which are elevated in many solid tumors and tumor infiltrates, to an orthoquinone chemical species that has direct cytotoxic effects on tumor cells. Preclinical studies have demonstrated that OXI-4503 has (i) single-agent activity against a range of xenograft tumor models; and (ii) synergistic or additive effects when incorporated in various combination regimens with chemotherapy, molecularly-targeted therapies (including tumor-angiogenesis inhibitors), and radiation therapy.
Indication
Investigated for use/treatment in cancer/tumors (unspecified).
Associated Conditions
No associated conditions information available.
Research Report
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): C18H22O12P2 [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
Clinical Trials
FDA Approved Products
Singapore Approved Products
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