[CAS NO. 109971-63-3] CombretastatinA-1
PRODUCTS SPECIFICATIONS [109971-63-3]
DESCRIPTION [109971-63-3]
Overview
| MDL | MFCD00877177 |
|---|---|
| Molecular Weight | 332.35 |
| Molecular Formula | C18H20O6 |
| SMILES | COC1=CC=C(/C=C\C2=CC(OC)=C(C(OC)=C2)OC)C(O)=C1O |
Summary
Combretastatin A-1 is a microtubule polymerization inhibitor that binds to the colchicine-binding site of tubulin. Combretastatin A-1 inhibits the Wnt/β-catenin pathway through tubulin depolymerization mediated AKT deactivation. Combretastatin A-1 exhibits anti-tumor and anti-vascular effects [1] [2] [3] .
IC50 & Target
Microtubule/Tubulin [1]
In Vitro
Combretastatin A-1 (72 h) inhibits the growth of various tumor cell lines in vitro, including HepG2, SMMC-7721, Hepa 1-6, LM-3, Bel-7402, Huh7, BGC-803, MDA-MB-231, MCF-7, A375, NCI-1975, CT-26, HT-29, A549 cells (IC
50
=9.2, 12.8, 32.9, 33.8, 38.4, 728.2, 12.2, 17.6, 46.0, 61.0, 256.3, 1075.0, 2082.0, 2247.0 nM, respectively)
[2]
.
Combretastatin A-1 (1-10 nM; 24 h) induces apoptosis by microtubule depolymerization-induced AKT inactivation and the removal of GSK-3β inhibition in HepG2 cells
[2]
.
Combretastatin A-1 (1-50 nM; 6 h) decreases the mitochondrial membrane potential (MMP) of HepG2 cells. Combretastatin A-1 shows dose-dependently ROS accumulation in HepG2 cells
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis [2]
| Cell Line: | HepG2 cells |
| Concentration: | 1, 5, 10 nM |
| Incubation Time: | 24 hours |
| Result: |
Significantly decreased Mcl-1 expression, but the Bcl-2 level was unchanged.
Reduced p-GSK 3β (Ser9) without altering total GSK-3β protein levels, indicating an activation of GSK-3β. Reduced AKT phosphorylation on Ser473 without an obvious change in the total AKT protein levels. |
In Vivo
Combretastatin A-1 (1-4 mg/kg; i.v. every other day for 4 weeks) significantly reduces the tumor volume in HepG2 subcutaneous xenograft model
[2]
.
Combretastatin A-1 (2 mg/kg; every other day for 21 days) shows enhanced apoptosis in orthotopic hepatocellular carcinoma mouse model
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Male athymic BALB/c nu/nu mice (16-18 g; 4-6 weeks old) were inoculated with HepG2 cells [2] |
| Dosage: | 1, 2, 4 mg/kg |
| Administration: | I.v. every other day for 4 weeks |
| Result: | Resulted in a significant tumor volume reduction at the dose of 2 mg/kg or 4 mg/kg. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00960557 | Mateon Therapeutics |
Neoplasm Metastasis
|
July 2009 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 100 mg/mL ( 300.89 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 3.0089 mL | 15.0444 mL | 30.0888 mL |
| 5 mM | 0.6018 mL | 3.0089 mL | 6.0178 mL |
| 10 mM | 0.3009 mL | 1.5044 mL | 3.0089 mL |
References
- [1] Pettit GR, et, al. Isolation, structure, and synthesis of combretastatins A-1 and B-1, potent new inhibitors of microtubule assembly, derived from Combretum caffrum. J Nat Prod. Jan-Feb 1987;50(1):119-31.
- [2] Mao J, et, al. Combretastatin A-1 phosphate, a microtubule inhibitor, acts on both hepatocellular carcinoma cells and tumor-associated macrophages by inhibiting the Wnt/β-catenin pathway. Cancer Lett. 2016 Sep 28;380(1):134-43.
- [3] Holwell SE, et, al. Anti-tumor and anti-vascular effects of the novel tubulin-binding agent combretastatin A-1 phosphate. Anticancer Res. Nov-Dec 2002;22(6C):3933-40.
Synonyms
