186497-07-4
中文名称
齐泊腾坦
英文名称
Zibotentan (ZD4054)
CAS
186497-07-4
分子式
C19H16N6O4S
分子量
424.43
MOL 文件
186497-07-4.mol
更新日期
2023/03/20 15:41:25
186497-07-4 结构式
基本信息
中文别名
赛博特坦齐泊腾坦
化合物ZIBOTENTAN
2-(4-(1,3,4-恶二唑-2-基)苯基)-N-(3-甲氧基-5-甲基吡嗪-2-基)吡啶-3-磺酰胺
N-(3-甲氧基-5-甲基-2-吡嗪基)-2-[4-(1,3,4-恶二唑-2-基)苯基]-3-吡啶磺酰胺
2-(4-(1,3,4-噁二唑-2-基)苯基)-N-(3-甲氧基-5-甲基吡嗪-2-基)吡啶-3-磺酰胺
英文别名
ZD454Zd4054
CS-558
Zd 4054
Zibotentan
Zibotentan(ZD4054)
zibotentan,CID 9910224
ZD4054
ZD-4054
ZD 4054
Zibotentan >=98% (HPLC)
ZIBOTENTAN (ZD4054) 250MG
所属类别
生物化工：Endothelin Receptor 拮抗剂物理化学性质
熔点239 - 241°C
沸点637.0±65.0 °C(Predicted)
密度1.422
储存条件Sealed in dry,Store in freezer, under -20°C
溶解度DMSO（少量）、甲醇（少量）
酸度系数(pKa)5.62±0.40(Predicted)
形态固体
颜色白色至灰白色
常见问题列表
生物活性
Zibotentan (ZD4054)是一种特异性的Endothelin (ET)A拮抗剂，IC50为21 nM，对ETB没有抑制活性。Phase 3。体外研究
As Zibotentan specifically inhibits ETA-mediated antiapoptotic effects, but not ETB-mediated proapoptotic effects in human and rat smooth muscle cells, Zibotentan binds to endothelin A receptor (ETA) with high affinity with Ki of 13 nM, and has no affinity for endothelin B receptor (ETB) with IC50 of >10 μM. Zibotentan treatment at 1 μM inhibits ET-1 induced mitogenic activity in ovarian carcinoma cell lines HEY and OVCA 433 secreting ET-1 and expressing ETA and ETB mRNA. ZD4054 (1 μM) inhibits ET-1 induced EGFR transactivation in HEY and OVCA 433 cells. Zibotentan (1 μM) reverts ET-1 mediated epithelial-mesenchymal transition (EMT), by enhancing E-cadherin expression and promoter activity, and inhibiting vascular endothelial growth factor (VEGF) secretion and invasiveness in HEY and OVCA 433 cells. Zibotentan also potently inhibits the basal and ET-1 induced cell proliferation in SKOV-3 and A-2780 cells, associated with the inhibition of AKT and p42/44MAPK phosphorylation, and with increased apoptosis through the inhibition of bcl-2 and activation of caspase-3 and poly(ADP-ribose) polymerase proteins.体内研究
Administration of Zibotentan at 10 mg/kg/day for 21 days potently inhibits the growth of HEY ovarian carcinoma xenografts in mice by 69% with no associated toxicity, which is in association with the blocking of cell proliferation evaluated by 37% inhibition of the Ki-67 expression, and the 62% inhibition of tumor-induced vascularization. Consistently, Zibotentan treatment significantly inhibits the expression of matrix metalloproteinase-2 (MMP-2) and VEGF, as well as the activation of p42/44 MAPK and EGFR, and potently enhances the expression of E-cadherin.靶点
| Target | Value |
| ET-A | 21 nM |
体外研究
在人和大鼠平滑肌细胞中，Zibotentan特异性抑制ET A 介导的抗凋亡作用，但是对ET B 介导的促凋亡作用没有影响，Zibotentan以高亲和力结合于内皮素A受体(ET A )，K i 为13 nM，而对内皮素B受体(ETB)没有亲和力，IC50>10 μM。在分泌ET-1，并表达ET A 与 ET B mRNA的卵巢癌细胞系HEY和OVCA 433中，1 μM Zibotentan处理抑制ET-1诱导的促有丝分裂活性。 ZD4054 (1 μM)抑制HEY和OVCA 433细胞中ET-1诱导的EGFR反式激活。HEY和OVCA 433细胞中，通过增强E-钙粘蛋白的表达和启动子活性，并抑制血管内皮生长因子(VEGF)分泌与侵袭，Zibotentan (1 μM)逆转ET-1介导的上皮-间质转化(EMT)。 Zibotentan也能有效抑制SKOV-3和A-2780细胞中基础和ET-1诱导的细胞增殖，这与AKT和p42/44MAPK磷酸化的抑制相关，也与通过bcl-2的抑制和caspase-3与聚(ADP-核糖)聚合酶蛋白质的激活，导致细胞凋亡增加相关。
体内研究
Zibotentan(10 mg/kg/day)给药21天有效抑制小鼠体内69%的HEY卵巢癌异种移植物的生长，而没有相关毒性，这与37% Ki-67表达和62%肿瘤诱导的血管形成被抑制表明的细胞增殖被阻断相关。同样地，Zibotentan治疗显著抑制基质金属蛋白酶-2 (MMP-2)和VEGF的表达，以及p42/44 MAPK与EGFR的活化，并有效增强E-钙粘蛋白的表达。