齐泊腾坦

生物活性体外研究体内研究生物活性靶点体外研究体内研究齐泊腾坦试剂级价格

齐泊腾坦

CAS号:186497-07-4
英文名:Zibotentan (ZD4054)
中文名:齐泊腾坦
CBNumber:CB31475871
分子式:C19H16N6O4S
分子量:424.43
MOL File:186497-07-4.mol

齐泊腾坦化学性质

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 (Sparingly), Methanol (Slightly)
形态 :Solid
酸度系数(pKa) :5.62±0.40(Predicted)
颜色 :White to Off-White

齐泊腾坦性质、用途与生产工艺

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 ET_A-mediated antiapoptotic effects, but not ET_B-mediated proapoptotic effects in human and rat smooth muscle cells, Zibotentan binds to endothelin A receptor (ET_A) with high affinity with K_i 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 ET_A and ET_B 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.
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。
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。