186497-07-4 Usage
Description
Zibotentan (ZD4054) is a selective antagonist of the endothelin (ET) receptor type A, with high specificity for the ETA receptor and minimal affinity for the ETB receptor. It is a promising pharmaceutical candidate for the treatment of various cancers, including prostate cancer and bone metastasis, due to its ability to inhibit the growth of cancer cells induced by endothelin 1 (ET-1) and reduce the expression of mediators involved in cell invasion and angiogenesis.
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 articles and documents
ETHANOLAMINE SALT OF N- (3-METHOXY-5-METHYLPYRAZIN-2YL) -2- (4- [1 , 3 , 4-0XADIAZ0LE-2-YL] PHENYL) PYRIDINE-3- SULPHONAMIDE
-
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.