Zibotentan (ZD4054)

Names

[ Name ]:
Zibotentan (ZD4054)

[Synonym ]:
N-(3-Methoxy-5-methyl-2-pyrazinyl)-2-[4-(1,3,4-oxadiazol-2-yl)phenyl]-3-pyridinesulfonamide
Zd 4054
S1456_Selleck
ZD4054
Zibotentan

Biological Activity

[Description]:

Zibotentan (ZD4054) is an orally administered, potent and specific ETA-receptor (endothelin A receptor) antagonist (IC50 = 21 nM). IC50 value: 21 nM Target: ETA receptorZibotentan is capable of inhibiting or reducing the multitude of effects that are evoked by ET-1 activation of the ETA receptor and which promote tumor survival, growth and progression. Zibotentan (ZD4054) treatment produced significant inhibition of tumor growth in ovarian and breast xenografts.

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> Endothelin Receptor

Research Areas >> Cancer

[References]

[1]. Zibotentan James, N.D., Growcott, J.W. Drugs Fut 2009, 34(8): 624.

[2]. Clarkson-Jones JA, Kenyon AS, Kemp J, Lenz EM, Oliver SD, Swaisland H.,Disposition and metabolism of the specific endothelin A receptor antagonist zibotentan (ZD4054) in healthy volunteers.,Xenobiotica. 2012 Apr;42(4):363-71. Epub 2011 Oct 20.

[3]. Li J, Liu Y, Qian J, Wu L, Kemp J, Nii M, Tomkinson H, Zuo Y, Ranson M, Usami M.,Single- and multiple-dose pharmacokinetics, safety and tolerability of zibotentan (ZD4054) in Chinese men with advanced solid tumors.,Cancer Chemother Pharmacol. 2012 Jul;70(

[4]. Nelson JB, Fizazi K, Miller K, Higano C, Moul JW, Akaza H, Morris T, McIntosh S, Pemberton K, Gleave M.,Phase 3, randomized, placebo-controlled study of zibotentan (ZD4054) in patients with castration-resistant prostate cancer metastatic to bone. ,Cancer

[5]. Tomkinson H, Kemp J, Oliver S, Swaisland H, Taboada M, Morris T.,Pharmacokinetics and tolerability of zibotentan (ZD4054) in subjects with hepatic or renal impairment: two open-label comparative studies.,BMC Clin Pharmacol. 2011 Mar 17;11:3.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
637.0±65.0 °C at 760 mmHg

[ Molecular Formula ]:
C₁₉H₁₆N₆O₄S

[ Molecular Weight ]:
424.433

[ Flash Point ]:
339.0±34.3 °C

[ Exact Mass ]:
424.095367

[ PSA ]:
141.37000

[ LogP ]:
2.38

[ Vapour Pressure ]:
0.0±1.9 mmHg at 25°C

[ Index of Refraction ]:
1.628

[ Storage condition ]:
-20°C

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302

[ Precautionary Statements ]:
P301 + P312 + P330

[ RIDADR ]:
NONH for all modes of transport

[ RTECS ]:
UT7937700

Articles

A phase I study of zibotentan (ZD4054) in patients with metastatic, castrate-resistant prostate cancer. Schelman WR et al

Invest. New Drugs 29(1) , 118-25, (2011)