Combretastatin A4 disodium phosphate

Fosbretabulin disodium(CA 4DP; CA 4P) is a microtubule destabilizing drug, a type of vascular-targeting agent, a drug designed to damage the vasculature (blood vessels) of cancer tumors causing central necrosis.IC50 Value: 4 nM [1]Target: microtubulein vitro: Cytotoxic IC(50) values of CA-4 in human bladder cancer cells were below 4 nM. Analyses of cell-cycle distribution showed CA-4 obviously induced G(2)-M phase arrest with sub-G(1) formation. The analyses of apoptosis showed that CA-4 induced caspase-3 activation and decreased BubR1 and Bub3 in cancer cells [1]. The enhanced apoptosis induced by dasatinib plus CA-4 was accompanied by a greater extent of mitochondrial depolarization, caspase-3 activation and PARP cleavage in HO-8910 cells. Furthermore, elevated expression of Mcl-1 led to a reduced apoptosis induced by dasatinib plus CA-4, highlighting that downregulated Mcl-1 was necessary for the potentiating effect of dasatinib to CA-4-triggered apoptosis [2].in vivo: The increased anticancer efficacy of dasatinib combined with CA-4 was further validated in a human HO-8910 ovarian cancer xenograft model in nude mice [2]. There was a significant, concentration dependent increase in mean arterial blood pressure with a maximum increase of about 60% of the baseline MAP at 30 mg/kg of CA4P compared to the saline control. However, there was no significant increase in the cardiac troponin I level after CA4P injection [3].Clinical trial: A phase II trial of fosbretabulin in advanced anaplastic thyroid carcinoma and correlation of baseline serum-soluble intracellular adhesion molecule-1 with outcome [4].

Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

Research Areas >> Cancer

[1]. Shen CH, Shee JJ, Wu JY, Combretastatin A-4 inhibits cell growth and metastasis in bladder cancer cells and retards tumour growth in a murine orthotopic bladder tumour model. Br J Pharmacol. 2010 Aug;160(8):2008-27.

[2]. Zhang C, Zhou SS, Li XR, Enhanced antitumor activity by the combination of dasatinib and combretastatin A-4 in vitro and in vivo. Oncol Rep. 2013 Jun;29(6):2275-82.

[3]. Ke Q, Bodyak N, Rigor DL, Pharmacological inhibition of the hypertensive response to combretastatin A-4 phosphate in rats. Vascul Pharmacol. 2009 Nov-Dec;51(5-6):337-43.

[4]. Mooney CJ, Nagaiah G, Fu P, A phase II trial of fosbretabulin in advanced anaplastic thyroid carcinoma and correlation of baseline serum-soluble intracellular adhesion molecule-1 with outcome. Thyroid. 2009 Mar;19(3):233-40.

Nocodazole | Monomethyl auristatin E | VcMMAE | Mertansine | Eribulin mesylate | Epothilone D | Vinorelbine (ditartrate) | epothilone B | McMMAF | MMAF (Hydrochloride) | Ixabepilone | Taltobulin | Estramustine phosphate sodium | Ansamitocin P-3 | Cevipabulin