In combination with sunitinib, combretastatin A1 phosphate (100 mg/kg; Ip; once at day 16 post-tumor induction) exhibits anti-tumor activity and anti-angiogenic effects on mouse tumors[2].

Animal/Disease Models: Male CBA mice (CRC liver metastasis)[2]
Doses: 100 mg/kg (received 40 mg/kg of Sunitinib daily from day 14 to 21 post tumor induction)
Route of Administration: Ip; once at day 16 post tumor induction
Experimental Results: Demonstrated a Dramatically diminished mean liver weight compared to livers from non tumor bearing animals, Dramatically decreased tumor vessels.

[1]. Patterson DM, et al. Phase I clinical and pharmacokinetic evaluation of the vascular-disrupting agent OXi4503 in patients with advanced solid tumors. Clin Cancer Res. 2012 Mar 1;18(5):1415-25.
[2]. Nguyen L, et al. Vascular disruptive agent OXi4503 and anti-angiogenic agent Sunitinib combination treatment prolong survival of mice with CRC liver metastasis. BMC Cancer. 2016 Jul 26;16:533.

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.
Combretastatin A1 Diphosphate is the diphosphate prodrug of the stilbenoid combretastatin A1, originally isolated from the plant Combretum caffrum, with vascular-disrupting and antineoplastic activities. Upon administration, combretastatin A1 diphosphate (CA1P) is dephosphorylated to the active metabolite combretastatin A1 (CA1), which promotes rapid microtubule depolymerization; endothelial cell mitotic arrest and apoptosis, destruction of the tumor vasculature, disruption of tumor blood flow and tumor cell necrosis may ensue. In addition, orthoquinone intermediates, metabolized from combretastatin A1 by oxidative enzymes found to be elevated in some tumor types, may bind to tumor cell thiol-specific antioxidant proteins and DNA, and stimulate oxidative stress by enhancing superoxide/hydrogen peroxide production. CA1 binds to tubulin at the same site as colchicine but with higher affinity.

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Drug Indication
Investigated for use/treatment in cancer/tumors (unspecified).

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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.

C18H22O12P2

492.31

492.059

288847-35-8

6918546

Typically exists as solid at room temperature

2.834

4

12

10

32

692

0

C1(OP(O)(O)=O)=C(/C=C\C2=CC(OC)=C(OC)C(OC)=C2)C=CC(OC)=C1OP(O)(O)=O

GSOXMQLWUDQTNT-WAYWQWQTSA-N

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-

[3-methoxy-2-phosphonooxy-6-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl] dihydrogen phosphate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 100 mg/mL (203.12 mM)

Solubility in Formulation 1: ≥ 5 mg/mL (10.16 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 5 mg/mL (10.16 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)