Zibotentan (ZD4054) Chemical Properties

Melting point:

239 - 241°C

Boiling point:

637.0±65.0 °C(Predicted)

Density 

1.422

storage temp. 

Sealed in dry,Store in freezer, under -20°C

solubility 

DMSO (Sparingly), Methanol (Slightly)

form 

Solid

pka

5.62±0.40(Predicted)

color 

White to Off-White

Zibotentan (ZD4054) Usage And Synthesis

Description

Zibotentan is a selective antagonist of the endothelin (ET) receptor type A (IC₅₀s = 21 and >10,000 nM for human recombinant ET_A and ET_B, respectively). It inhibits growth of HEY, OVCA 433, SKOV3, and A2780 cells induced by endothelin 1 (ET-1; ) in vitro. Zibotentan reduces ET-1-induced expression of MMP-2, MMP-9, VEGF, COX-1 and COX-2, mediators of cell invasion and angiogenesis, in HEY cells. In vivo, zibotentan (10-50 mg/kg per day) reduces tumor growth in an HEY mouse xenograft model in a dose-dependent manner. Formulations containing zibotentan are under clinical investigation for the treatment of ovarian and castration-resistant prostate cancers.

Uses

Zibotentan is a specific endothelin-A receptor antagonist that is a potential candidate in the treatment of prostate cancer, bone metastasis and various other types of cancer.

Definition

ChEBI: N-(3-methoxy-5-methyl-2-pyrazinyl)-2-[4-(1,3,4-oxadiazol-2-yl)phenyl]-3-pyridinesulfonamide is a phenylpyridine.

in vitro

in the human ovarian cancer etar positive cell lines, zd4054 effectively inhibited the basal and et-1-induced cell proliferation, with the inhibition of akt and p42/44mapk phosphorylation, and increased apoptosis, through the inhibition of bcl-2 and activation of caspase-3 and poly(adp-ribose) polymerase proteins. [1].

in vivo

in hey ovarian cancer xenografts, zd4054 inhibited tumor growth to the same degree as paclitaxel. moreover, zd4054-dependent tumor growth inhibition was associated with a reduction in proliferation index, mmp-2 expression, and microvessel microvessel density [2].

target

ETA

References

[1] morris cd, rose a, curwen j, hughes am, wilson dj, webb dj. specific inhibition of the endothelin a receptor with zd4054: clinical and pre-clinical evidence. br j cancer. 2005 jun 20;92(12):2148-52.
[2] rosanò l, di castro v, spinella f, nicotra mr, natali pg, bagnato a. zd4054, a specific antagonist of the endothelin a receptor, inhibits tumor growth and enhances paclitaxel activity in human ovarian carcinoma in vitro and in vivo. mol cancer ther. 2007 jul;6(7):2003-11.
[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(1):57-63.

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