186497-07-4 Usage
Uses
Used in Oncology:
Zibotentan (ZD4054) is used as an anticancer agent for the treatment of prostate cancer, bone metastasis, and various other types of cancer. It functions by specifically targeting the endothelin-A receptor, thereby inhibiting the growth of cancer cells induced by ET-1 and reducing the expression of matrix metalloproteinases (MMP-2 and MMP-9), vascular endothelial growth factor (VEGF), cyclooxygenase-1 (COX-1), and cyclooxygenase-2 (COX-2), which are key mediators of cell invasion and angiogenesis.
Used in Clinical Research:
Formulations containing Zibotentan (ZD4054) are under clinical investigation for the treatment of ovarian and castration-resistant prostate cancers. In vivo studies have demonstrated that Zibotentan reduces tumor growth in an HEY mouse xenograft model in a dose-dependent manner, indicating its potential effectiveness in treating these types of cancers.
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].
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.
Check Digit Verification of cas no
The CAS Registry Mumber 186497-07-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,8,6,4,9 and 7 respectively; the second part has 2 digits, 0 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 186497-07:
(8*1)+(7*8)+(6*6)+(5*4)+(4*9)+(3*7)+(2*0)+(1*7)=184
184 % 10 = 4
So 186497-07-4 is a valid CAS Registry Number.
186497-07-4Relevant academic research and scientific papers
ETHANOLAMINE SALT OF N- (3-METHOXY-5-METHYLPYRAZIN-2YL) -2- (4- [1 , 3 , 4-0XADIAZ0LE-2-YL] PHENYL) PYRIDINE-3- SULPHONAMIDE
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Page/Page column 6; 20, (2010/11/25)
N-(Methoxy-5-methylpyrazin-2-yl)-2-(4-[1 ,3,4-oxadiazol-yl]phenyl)pyridine-3- sulphonamide ethanolamine salt its synthesis and its uses are described.
Heterocyclic compounds
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, (2008/06/13)
The invention concerns pharmaceutically useful compounds of the formula I, in which A1, A2, A3, A4, B1, m, Ar, W, X, Y, Z and R1 have any of the meanings defined herein, and their pharmaceutically acceptable salts, and pharmaceutical compositions containing them. The novel compounds possess endothelin receptor antagonist activity and are useful, for example, in the treatment of diseases or medical conditions in which elevated or abnormal levels of endothelin play a significant causative role. The invention further concerns processes for the manufacture of the novel compounds and the use of the compounds in medical treatment.
