CAS 168555-66-6|Combretastatin A4 disodium phosphate

Introduction：Basic information about CAS 168555-66-6|Combretastatin A4 disodium phosphate, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Combretastatin A4 disodium phosphate BiologicalActivity
3. Chemical & Physical Properties
4. Safety Information
5. Synonyms

Common Name	Combretastatin A4 disodium phosphate
CAS Number	168555-66-6	Molecular Weight	440.292
Density	/	Boiling Point	611.8ºC at 760 mmHg
Molecular Formula	C₁₈H₁₉Na₂O₈P	Melting Point	238-242ºC
MSDS	ChineseUSA	Flash Point	/

Names

Name	disodium,[2-methoxy-5-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl] phosphate
Synonym	More Synonyms

Combretastatin A4 disodium phosphate BiologicalActivity

Description	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].
Related Catalog	Signaling Pathways >>Cell Cycle/DNA Damage >>Microtubule/TubulinSignaling Pathways >>Cytoskeleton >>Microtubule/TubulinResearch Areas >>Cancer
References	[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.

Description

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].

Related Catalog

Signaling Pathways >>Cell Cycle/DNA Damage >>Microtubule/TubulinSignaling Pathways >>Cytoskeleton >>Microtubule/TubulinResearch Areas >>Cancer

References

[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.

Chemical & Physical Properties

Boiling Point	611.8ºC at 760 mmHg
Melting Point	238-242ºC
Molecular Formula	C₁₈H₁₉Na₂O₈P
Molecular Weight	440.292
Exact Mass	440.061279
PSA	119.15000
LogP	4.23930
Vapour Pressure	7.99E-16mmHg at 25°C
InChIKey	SFKGCTYUWCBOHY-YSMBQZINSA-N
SMILES	COc1ccc(C=Cc2cc(OC)c(OC)c(OC)c2)cc1OP(=O)(O)O.[Na]
Storage condition	Refrigerator
Water Solubility	H2O: soluble5mg/mL, clear

Safety Information

Hazard Codes	Xi
RIDADR	NONH for all modes of transport

Synonyms

Fosbretabulin disodium

Phenol, 2-methoxy-5-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]-, dihydrogen phosphate, sodium salt (1:2)

Fosbretabulin disodium (USAN)

Fosbretabulin (Combretastatin A4 Phosphate (CA4P)) Disodium

Combretastatin A-4 phosphate

Zybrestat

Disodium 2-methoxy-5-[(E)-2-(3,4,5-trimethoxyphenyl)vinyl]phenyl phosphate

CA4DP

Combretastatin A4 disodium phosphate

Fosbretabulin (disodium)

CoMbretastatin A4 Phosphate DisodiuM Salt

Recommended......