Combretastatin A-4

Combretastatin A-4 is a combretastatin and a stilbenoid. It can be isolated from Combretum afrum, the Eastern Cape South African bushwillow tree or in Combretum leprosum, the mofumbo, a species found in Brazil.^[3][4]

Combretastatin A-4

Names
Preferred IUPAC name 2-Methoxy-5-[(1Z)-2-(3,4,5-trimethoxyphenyl)ethen-1-yl]phenol
Other names Combretastatin A4 CA-4 1-(3,4,5-Trimethoxyphenyl)-2-(3′-hydroxy-4′-methoxyphenyl)ethene 3,4,5-Trimethoxy-3′-hydroxy-4′-methoxystilbene
Identifiers
CAS Number	117048-59-6 Y
3D model (JSmol)	Interactive image
ChEMBL	ChEMBL67 Y
ChemSpider	4508364 Y
ECHA InfoCard	100.159.667
PubChem CID	5351344
UNII	16U6OP69RQ Y
CompTox Dashboard (EPA)	DTXSID101025983
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- Y Key: HVXBOLULGPECHP-WAYWQWQTSA-N Y
SMILES COC1=C(C=C(C=C1)C=CC2=CC(=C(C(=C2)OC)OC)OC)O
Properties
Chemical formula	C18H20O5
Molar mass	316.34 g/mol
Melting point	116 °C (241 °F; 389 K)[1]
Solubility in water	insoluble
Solubility in DMSO, Ethanol	DMSO : 63 mg/mL, Ethanol : 34 mg/mL[2]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is YN ?) Infobox references

Function

Tubulin represents a potent target in cancer chemotherapy, given its role in cell division. Combretastatin is a naturally occurring well known tubulin polymerization inhibitor. Combretastatin A-4 comes in two stereoisomers (cis (shown top right), and trans); The cis form binds much better to the 'colchicine' site on tubulin to inhibit polymerization.^[5]

Derivatives

Combretastatin A-4 is the active component of combretastatin A-4 phosphate, a prodrug designed to damage the vasculature (blood vessels) of cancer tumors causing central necrosis.^{[citation needed]}

A large number of synthetic derivatives have been reported,^[6][7] including beta-lactam based compounds.^[8]

Pharmacokinetics

CA4 has a half life of 1.8-4.2h in humans. CA4P(a prodrug) has a half life of 0.22-0.36h in humans.^[9]

See also

• Ombrabulin, a combretastatin A-4 derivative in clinical trials for treatment of cancer