168555-66-6 Usage
Chemical Properties
White Solid
Uses
Phosphorylated Combretastatin, a small organic molecule found in the bark of the African bush willow tree Combretum caffrum. Combretastatin-A4 Prodrug Induces Mitotic Catastrophe in Chronic Lymphocytic Leukemia Cell Line Independent of Caspase Activation and Poly(ADP-ribose) Polymerase Cleavage. A potent cytotoxic agent which strongly inhibits the polymerization of tubulin by binding to the colchicine site.
Biological Activity
fosbretabulin (combretastatin a4 phosphate (ca4p)) disodium is a microtubule destabilizing drug, a water-soluble prodrug of combretasain a4(ca4) and a tumor vascular-targeting agent.microtubule is the cylindrical and filamentous structure that required for cell shape, migration, cilia and flagella mobility etc. tubulin is the major component of microtubulesin proliferative endothelial cells, ca4p (dose less than 1/10 of the max. tolerated dose) leaded to tumor vascular shutdown, and short drug exposure of ca4p caused significant long-term anti-proliferative and cytotoxic effects. [1] in ca40 treated endothelia cell, myosin light chain was phosphorylated and lead to actinomyosin contractility, assembly of actin stress fibers and focal adhesions formation. [2] in huvec cells, ca4p blocked growth factor–induced endothelial cell proliferation and migration and impaired capillary tube formation. [3]in c57bl/6 mice, ca4p treatment in combination with mab against ve-cardherin facilitated b16 melanoma tumor necrosis and inhibited tumor neoangionesis. [3] in human breast cancer models in vivo, 6 hours after ca4p administration showed a 93% decreased functional vascular volume and lasted over the next 12 hours. [1]
Biochem/physiol Actions
Fosbretabulin disodium (Combretastatin A4 phosphate, CA4P) is a potent vascular-disrupting agent (VDA). Fosbretabulin disodium is a prodrug that is converted to combretastatin A (Sigma Cat No. C7744) inside the endothelial cells that line blood vessels, where it binds to tubulin dimers and prevents microtubule polymerization, resulting in mitotic arrest and apoptosis in endothelial cells. Fosbretabulin disodium is a potent anti-cancer agent that exhibits antivascular effects on tumor vasculature, inducing a rapid reduction in tumor blood flow and a concomitant increase of cellular necrosis. Some of its activity is believed to involve interference with vascular endothelial-cadherin signaling in addition to its microtubule-disrupting activity.
references
[1] dark gg, hill sa, prise ve, tozer gm, pettit gr, chaplin dj. combretastatin a-4, an agent that displays potent and selective toxicity toward tumor vasculature. cancer res. 1997 may 15;57(10):1829-34.[2] kanthou c, tozer gm. the tumor vascular targeting agent combretastatin a-4-phosphate induces reorganization of the actin cytoskeleton and early membrane blebbing in human endothelial cells. blood. 2002 mar 15;99(6):2060-9.[3] vincent l, kermani p, young lm, cheng j, zhang f, shido k, lam g, bompais-vincent h, zhu z, hicklin dj, bohlen p, chaplin dj, may c, rafii s. combretastatin a4 phosphate induces rapid regression of tumor neovessels and growth through interference with vascular endothelial-cadherin signaling. j clin invest. 2005 nov;115(11):2992-3006.
Check Digit Verification of cas no
The CAS Registry Mumber 168555-66-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,6,8,5,5 and 5 respectively; the second part has 2 digits, 6 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 168555-66:
(8*1)+(7*6)+(6*8)+(5*5)+(4*5)+(3*5)+(2*6)+(1*6)=176
176 % 10 = 6
So 168555-66-6 is a valid CAS Registry Number.
InChI:InChI=1/C18H21O8P.2Na/c1-22-14-8-7-12(9-15(14)26-27(19,20)21)5-6-13-10-16(23-2)18(25-4)17(11-13)24-3;;/h5-11H,1-4H3,(H2,19,20,21);;/q;2*+1/p-2/b6-5-;;
