齐泊腾坦

齐泊腾坦

中文名称齐泊腾坦
中文同义词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;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;齐泊腾坦;赛博特坦;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
英文名称Zibotentan (ZD4054)
英文同义词N-(3-METHOXY-5-METHYLPYRAZIN-2-YL)-2-[4-(1,3,4-OXADIAZOL-2-YL)PHENYL]PYRIDINE-3-SULFONAMIDE;3-Pyridinesulfonamide, N-(3-methoxy-5-methylpyrazinyl)-2-(4-(1,3,4-oxadiazol-2-yl)phenyl)-;Zd 4054;Zd4054;Zibotentan;Zibotentan(ZD4054);N-(3-Methoxy-5-methyl-2-pyrazinyl)-2-[4-(1,3,4-oxadiazol-2-yl)phenyl]-3-pyridinesulfonamide;2-(4-(1,3,4-oxadiazol-2-yl)phenyl)-N-(3-Methoxy-5-Methylpyrazin-2-yl)pyridine-3-sulfonaMide
CAS号186497-07-4
分子式C19H16N6O4S
分子量424.43
EINECS号
相关类别G蛋白偶联受体&G蛋白;小分子抑制剂,天然产物;Inhibitors
Mol文件186497-07-4.mol
结构式齐泊腾坦 结构式

齐泊腾坦 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)
形态固体
酸度系数(pKa)5.62±0.40(Predicted)
颜色白色至类白色

齐泊腾坦 用途与合成方法

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。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.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.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。
TargetValue
ET-A 21 nM

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。

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。

安全信息

MSDS信息

更新日期产品编号产品名称CAS号包装价格
2024/01/25HY-10088Zibotentan1 mg477元
2024/01/25HY-10088齐泊腾坦
Zibotentan
186497-07-45mg1050元

齐泊腾坦 上下游产品信息

"齐泊腾坦"相关产品信息
马西替坦 阿瑞吡坦 依伐卡托 Sitaxentansodium 恩替诺特 雷帕霉素 Zibotentan(ZD4054)
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