Combretastatin A1 phosphate (Oxi4503; CA1P; Combretastatin A1 diphosphate)   中文名称: 考布他汀A1磷酸盐

与舒尼替尼联合使用，考布他汀 A1 磷酸盐（100 mg/kg；Ip；肿瘤诱导后第 16 天一次）对小鼠肿瘤表现出抗肿瘤活性和抗血管生成作用[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 currently undergoing clinical trials for the treatment of cancer/tumor. OXI-4503 is a solid drug. OXI-4503 blocks and disrupts tumor angiogenesis, leading to widespread tumor cell death and necrosis. OXI-4503 (combretastatin A1 diphosphate/CA1P) is a unique and highly potent dual-mechanism angiogenesis disruptor (VDA). Furthermore, preclinical data indicate that OXI-4503 is metabolized by oxidases such as tyrosinase and peroxidase, which are highly expressed in many solid tumors and tumor infiltrations. The metabolites, orthoquinone compounds, have direct cytotoxic effects on tumor cells. Preclinical studies have shown that OXI-4503 has the following effects: (i) single-agent activity in various xenograft tumor models; (ii) synergistic or additive effects when used in combination with chemotherapy, molecularly targeted therapy (including tumor angiogenesis inhibitors), and radiotherapy.
Combrestatin A1 diphosphate is a diphosphate prodrug of the stilbene compound combrestatin A1, originally isolated from the plant Combretum caffrum, and possesses angiogenic and antitumor activities. After administration, combrestatin A1 diphosphate (CA1P) is dephosphorylated to the active metabolite combrestatin A1 (CA1), which promotes rapid microtubule depolymerization; this may lead to endothelial cell mitotic arrest and apoptosis, tumor angiogenesis, tumor blood flow disruption, and tumor cell necrosis. Furthermore, the ortho-quinone intermediate produced by the oxidase metabolism of combrestatin A1 (increased in certain tumor types) may bind to thiol-specific antioxidant proteins and DNA in tumor cells, stimulating oxidative stress by enhancing superoxide/hydrogen peroxide production. CA1 binds to tubulin at the same site as colchicine, but with a higher affinity.
Drug Indications
It has been studied for the treatment of cancer/tumors (not specified).

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Mechanism of Action
OXi4503 blocks and disrupts tumor blood vessels, leading to widespread tumor cell death and necrosis. It induces tumor vasoconstriction, with less impact on the peripheral region of the tumor than on the central region.

C18H22O12P2

492.31

492.059

288847-35-8

6918546

Typically exists as solid at room temperature

2.834

190.06

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

注意： 本产品在运输和储存过程中需避光。

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)

配方 1 中的溶解度: ≥ 5 mg/mL (10.16 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 50.0 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 5 mg/mL (10.16 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 50.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。