Combretastatin A4 is a microtubule-targeting agent that binds β-tubulin with Kd of 0.4 μM.

Product information

CAS Number: 117048-59-6

Molecular Weight: 316.35

Formula: C18H20O5

Synonym:

CRC 87-09

Chemical Name: 2-methoxy-5-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenol

Smiles: COC1C=C(C=C(OC)C=1OC)/C=C\C1C=C(O)C(=CC=1)OC

InChiKey: HVXBOLULGPECHP-WAYWQWQTSA-N

InChi: InChI=1S/C18H20O5/c1-20-15-8-7-12(9-14(15)19)5-6-13-10-16(21-2)18(23-4)17(11-13)22-3/h5-11,19H,1-4H3/b6-5-

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 100 mg/mL (316.11 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Combretastatin A4 phosphate (≥ 50 µM) significantly increases the percentage of annexin-V-binding cells and significantly decreases forward scatter. Combretastatin A4 phosphate does not appreciably increase hemolysis. Hundred µM Combretastatin A4 phosphate significantly increases Fluo3-fluorescence. The effect of Combretastatin A4 phosphate (100 µM) on annexin-V-binding is significantly blunted, but not abolished, by removal of extracellular Ca2+. Combretastatin A4 phosphate (≥ 50 µM) significantly decreases GSH abundance and ATP levels but does not significantly increase ROS or ceramide. Polymersomes co-encapsulating doxorubicin-combretastatin-A4 phosphate (1:10) shows strong synergistic cytotoxicity against human nasopharyngeal epidermal carcinoma (KB) cells. Pretreatment with Combretastatin A4 phosphate does not influence the amount of VM in 3-D culture as well as the expression of these key molecules.

In Vivo:

DBP and MBP at 30 minutes after administration are higher in rats treated with Combretastatin A4 disodium phosphate 120 mg/10 mL/kg. The toxicokinetic parameters of Combretastatin A4 phosphate and Combretastatin A4 in rats treated with Combretastatin A4 disodium phosphate 120 mg/10 mL/kg are indicated, and the values of Cmax, T1/2, and AUC0-inf for Combretastatin A4 are 156±13 μM, 5.87±1.69 h, and 89.4±10.1 h·μM, respectively. In vivo, W256 tumors show marked intratumoral hypoxia after Combretastatin A4 phosphate treatment, accompanied by increased VM formation. Combretastatin A4 phosphate exhibits only a delay in tumor growth within 2 days but rapid tumor regrowth afterward. VM density is positively related to tumor volume and tumor weight at day 8. Combretastatin A4 phosphate causes hypoxia which induces VM formation in W256 tumors through HIF-1α/EphA2/PI3K/matrix metalloproteinase (MMP) signaling pathway, resulting in the consequent regrowth of the damaged tumor.

References:

1. Tochinai R, et al. Combretastatin A4 disodium phosphate-induced myocardial injury. J Toxicol Pathol. 2016 Jul;29(3):163-71.
2. Signoretto E, et al. Stimulation of Eryptosis by Combretastatin A4 Phosphate Disodium (CA4P). Cell Physiol Biochem. 2016;38(3):969-8
3. Zhu J, et al. Co-Encapsulation of Combretastatin-A4 Phosphate and Doxorubicin in Polymersomes for Synergistic Therapy of Nasopharyngeal Epidermal Carcinoma. J Biomed Nanotechnol. 2015 Jun;11(6):997-1006.

Products are for research use only. Not for human use.