Combretastatin A4

Catalog No.S7783 Batch:S778301

Technical Data

Formula	C₁₈H₂₀O₅
Molecular Weight	316.35	CAS No.	117048-59-6
Solubility (25°C)*	In vitro	DMSO	63 mg/mL (199.14 mM)
		Ethanol	34 mg/mL (107.47 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

Combretastatin A4 is a microtubule-targeting agent that binds β-tubulin with K_d of 0.4 μM.Phase 3.

Targets

β-tubulin ^[1]

0.4 μM(Kd)

In vitro

Combretastatin A4 inhibits the growth of MDA-MB-231, A549, Hela, HL-60, SF295, HCT-8, MDA-MB435, PC3M, OVCAR-8, NCI-H358M, and lymphocyte cells with IC50 of 2.8, 3.8, 0.9, 2.1, 6.2, 5.3, 7.9, 4.7, 0.37, 8, and 3.2 nM, respectively.^[1] ^[2] 1 μM Combretastatin A4 inhibits tubulin polymerization by 35%, and 10 μM nearly completely blocks tubulin polymerization. Combretastatin A4 demonstrates great relative binding capacity, reaching 78% of colchicine binding.^[1]

In vivo

In NT2 and MDA-MB-231 mammary tumor model, administration of Combretastatin A4 (100 mg/kg, i.p.) induces a significant decrease in lipids R1 and a reduction in tumor pO2 measured by electron paramagnetic resonance (EPR) oximetry.^[2] Combretastatin A4 (100 mg/kg, i.p.) significant decreases the K^trans in male NMRI mice.^[3]

Protocol (from reference)

Kinase Assay:^{^[1]}	Competitive binding assay using LC-MS/MS Colchicine (1.2 μ M) is incubated with tubulin (1.3 mg/mL) in the incubation buﬀer (80 mM PIPES, 2.0 mM MgCl2, 0.5 mM EGTA, pH 6.9) at 37℃ for 1 h. Varying concentrations (0.1 − 125 μ M) of Combretastatin A4 are used to compete with colchicine originally bound to tubulin. After incubation, the ﬁltrate is obtained. The ability of the analogue to inhibit the binding of colchicine is expressed as a percentage of control binding in the absence of any competitor.
Cell Assay:^{^[1]}	Cell lines MDA-MB-231, A549, and Hela cells Concentrations ~3.8 nM Incubation Time 72 h Method MDA-MB-231, A549, and HeLa cells are grown in DMEM medium (115 units/mL of penicillin G, 115 μg/mL of streptomycin, and 10% fetal bovine serum). Cells are seeded in 96-well plates (5000 cells/well) containing 50 μL of growth medium for 24 h. After medium removal, 100 μL of fresh medium containing individual analogue compounds at diﬀerent concentrations is added to each well and incubated at 37 ℃ for 72 h. After 24 h of culture, the cells are supplemented with 50 μL of analogue compounds dissolved in DMSO (less than 0.25% in each preparation). After 72 h of incubation, 20 μL of resazurin is added for 2 h before recording ﬂuorescence at 560 nm (excitation) and 590 nm (emission) using a Victor microtiter plate ﬂuorimeter. The IC50 is deﬁned as the compound concentration required to inhibit cell proliferation by 50% in comparison with cells treated with the maximum amount of DMSO (0.25%) and considered as 100% viability.
Animal Study:^{^[2]}	Animal Models FVB/N or nude NMRI female mice bearing NT2 and MDA-MB-231 tumors Dosages 100 mg/kg Administration i.p.

References

Selleck's Combretastatin A4 has been cited by 6 publications

Mechanism of ribosome-associated mRNA degradation during tubulin autoregulation [ Mol Cell, 2023, 83(13):2290-2302.e13]	PubMed: 37295431
Mechanism of ribosome-associated mRNA degradation during tubulin autoregulation [ Mol Cell, 2023, 83(13):2290-2302.e13]	PubMed: 37295431
Targeting MCL-1 triggers DNA damage and an anti-proliferative response independent from apoptosis induction [ Cell Rep, 2023, 42(10):113176]	PubMed: 37773750
Rigosertib induces mitotic arrest and apoptosis in RAS-driven rhabdomyosarcoma and neuroblastoma [ Mol Cancer Ther, 2020, molcanther.0525.2020]	PubMed: 33158997
The Natural Compound Withaferin A Covalently Binds to Cys239 of β-Tubulin to Promote Tubulin Degradation. [ Mol Pharmacol, 2019, 96(6):711-719]	PubMed: 31585985
Evaluation of the antitumor activity of NOV202, a novel microtubule targeting and vascular disrupting agent [Rickardson L, et al. Drug Des Devel Ther, 2017, 11:1335-1351]	PubMed: 28496304

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SHIPPING AND STORAGE
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