Identification
- Generic Name
- OXI-4503
- DrugBank Accession Number
- DB05143
- 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.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for OXI-4503 (DB05143)
- Weight
- Average: 492.31
Monoisotopic: 492.058650144 - Chemical Formula
- C18H22O12P2
- Synonyms
- CA1P
- Combretastatin A-1 bis(phosphate)
- Combretastatin A1 diphosphate
- OXI4503
Pharmacology
- Indication
Investigated for use/treatment in cancer/tumors (unspecified).
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OXi4503 blocks and destroys tumor vasculature, resulting in extensive tumor cell death and necrosis. In addition, however, preclinical data demonstrates that OXi4503 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.
- Mechanism of action
OXi4503 blocks and destroys tumor vasculature, resulting in extensive tumor cell death and necrosis. It induced the shutdown of tumor blood vessels and affected peripheral tumor regions less than central regions.
- Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAluminum hydroxide Aluminum hydroxide can cause a decrease in the absorption of OXI-4503 resulting in a reduced serum concentration and potentially a decrease in efficacy. Calcium acetate Calcium acetate can cause a decrease in the absorption of OXI-4503 resulting in a reduced serum concentration and potentially a decrease in efficacy. Calcium carbonate Calcium carbonate can cause a decrease in the absorption of OXI-4503 resulting in a reduced serum concentration and potentially a decrease in efficacy. Calcium chloride Calcium chloride can cause a decrease in the absorption of OXI-4503 resulting in a reduced serum concentration and potentially a decrease in efficacy. Calcium citrate Calcium citrate can cause a decrease in the absorption of OXI-4503 resulting in a reduced serum concentration and potentially a decrease in efficacy. Calcium glucoheptonate Calcium glucoheptonate can cause a decrease in the absorption of OXI-4503 resulting in a reduced serum concentration and potentially a decrease in efficacy. Calcium gluconate Calcium gluconate can cause a decrease in the absorption of OXI-4503 resulting in a reduced serum concentration and potentially a decrease in efficacy. Calcium lactate Calcium lactate can cause a decrease in the absorption of OXI-4503 resulting in a reduced serum concentration and potentially a decrease in efficacy. Calcium Phosphate Calcium Phosphate can cause a decrease in the absorption of OXI-4503 resulting in a reduced serum concentration and potentially a decrease in efficacy. Calcium polycarbophil Calcium polycarbophil can cause a decrease in the absorption of OXI-4503 resulting in a reduced serum concentration and potentially a decrease in efficacy. 
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- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key OXI-4503 dipotassium Q9F7QEH36F 1014615-46-3 IQYUGENRXZHYER-XNOMRPDFSA-L
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
- Kingdom
- Organic compounds
- Super Class
- Phenylpropanoids and polyketides
- Class
- Stilbenes
- Sub Class
- Not Available
- Direct Parent
- Stilbenes
- Alternative Parents
- Phenyl phosphates / Styrenes / Phenoxy compounds / Methoxybenzenes / Anisoles / Alkyl aryl ethers / Organic oxides / Hydrocarbon derivatives
- Substituents
- Alkyl aryl ether / Anisole / Aromatic homomonocyclic compound / Aryl phosphate / Aryl phosphomonoester / Benzenoid / Ether / Hydrocarbon derivative / Methoxybenzene / Monocyclic benzene moiety
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- JH6Z94GLUD
- CAS number
- 288847-35-8
- InChI Key
- GSOXMQLWUDQTNT-WAYWQWQTSA-N
- InChI
- InChI=1S/C18H22O12P2/c1-25-13-8-7-12(16(29-31(19,20)21)18(13)30-32(22,23)24)6-5-11-9-14(26-2)17(28-4)15(10-11)27-3/h5-10H,1-4H3,(H2,19,20,21)(H2,22,23,24)/b6-5-
- IUPAC Name
- [3-methoxy-2-(phosphonooxy)-6-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenoxy]phosphonic acid
- SMILES
- [H]\C(=C(/[H])C1=C(OP(O)(O)=O)C(OP(O)(O)=O)=C(OC)C=C1)C1=CC(OC)=C(OC)C(OC)=C1
References
- General References
- Chan LS, Malcontenti-Wilson C, Muralidharan V, Christophi C: Alterations in vascular architecture and permeability following OXi4503 treatment. Anticancer Drugs. 2008 Jan;19(1):17-22. [Article]
- Hokland SL, Horsman MR: The new vascular disrupting agent combretastatin-A1-disodium-phosphate (OXi4503) enhances tumour response to mild hyperthermia and thermoradiosensitization. Int J Hyperthermia. 2007 Nov;23(7):599-606. [Article]
- Chan LS, Malcontenti-Wilson C, Muralidharan V, Christophi C: Effect of vascular targeting agent Oxi4503 on tumor cell kinetics in a mouse model of colorectal liver metastasis. Anticancer Res. 2007 Jul-Aug;27(4B):2317-23. [Article]
- Salmon HW, Siemann DW: Effect of the second-generation vascular disrupting agent OXi4503 on tumor vascularity. Clin Cancer Res. 2006 Jul 1;12(13):4090-4. [Article]
- External Links
- PubChem Compound
- 6918546
- PubChem Substance
- 175426952
- ChemSpider
- 5293743
- BindingDB
- 50236033
- ChEMBL
- CHEMBL1205402
- ZINC
- ZINC000003994214
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 1 Completed Treatment Metastatic Cancer 1 1 Completed Treatment Solid Tumors 1 1 Terminated Treatment Acute Myeloid Leukemia / Myelodysplastic Syndrome 1 1, 2 Unknown Status Treatment Acute Myeloid Leukemia / Myelodysplastic Syndrome 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0268 mg/mL ALOGPS logP 1.76 ALOGPS logP 1.77 Chemaxon logS -4.3 ALOGPS pKa (Strongest Acidic) 1.31 Chemaxon pKa (Strongest Basic) -4.3 Chemaxon Physiological Charge -4 Chemaxon Hydrogen Acceptor Count 10 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 170.44 Å2 Chemaxon Rotatable Bond Count 10 Chemaxon Refractivity 113.07 m3·mol-1 Chemaxon Polarizability 43.31 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.8178 Blood Brain Barrier + 0.9392 Caco-2 permeable + 0.5621 P-glycoprotein substrate Non-substrate 0.6563 P-glycoprotein inhibitor I Inhibitor 0.5894 P-glycoprotein inhibitor II Non-inhibitor 0.7451 Renal organic cation transporter Non-inhibitor 0.9072 CYP450 2C9 substrate Non-substrate 0.7647 CYP450 2D6 substrate Non-substrate 0.7938 CYP450 3A4 substrate Substrate 0.5659 CYP450 1A2 substrate Inhibitor 0.5726 CYP450 2C9 inhibitor Non-inhibitor 0.7198 CYP450 2D6 inhibitor Non-inhibitor 0.9068 CYP450 2C19 inhibitor Inhibitor 0.5589 CYP450 3A4 inhibitor Inhibitor 0.505 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6137 Ames test Non AMES toxic 0.8531 Carcinogenicity Non-carcinogens 0.6756 Biodegradation Not ready biodegradable 0.7566 Rat acute toxicity 2.6950 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7806 hERG inhibition (predictor II) Non-inhibitor 0.8709
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Drug created at October 21, 2007 22:23 / Updated at June 12, 2020 16:52