4-(4-氯苯基)-4-[4-(1H-吡唑-4-基)苯基]哌啶二盐酸盐
4-(4-氯苯基)-4-[4-(1H-吡唑-4-基)苯基]哌啶二盐酸盐
4-(4-氯苯基)-4-[4-(1H-吡唑-4-基)苯基]哌啶二盐酸盐 用途与合成方法
Akt1 32 nM (IC 50 ) |
Akt2 17 nM (IC 50 ) |
Akt3 47 nM (IC 50 ) |
PKA 20 nM (IC 50 ) |
The inhibition of AKT2 by AT7867 is shown to be ATP-competitive with a K i of 18nM. AT7867 also displays potent activity against the structurally related AGC kinases p70S6K and PKA, but shows a clear window of selectivity against kinases from other kinase sub-families. In vitro growth inhibition studies show that AT7867 blocks proliferation in a number of human cancer cell lines. AT7867 appears to be most potent at inhibiting proliferation in MES-SA uterine, MDA-MB-468 and MCF-7 breast, and HCT116 and HT29 colon lines (IC 50 values range from 0.9-3 μM), and least effective in the two prostate lines tested (IC 50 values range from 10-12 μM) .
Following oral administration at 20 mg/kg, the elimination of AT7867 from plasma appears to be similar to that observed after i.v. administration. Plasma levels of AT7867 remain above 0.5 μM for at least 6 hours following an oral dose of 20 mg/kg. Assuming linear pharmacokinetics following i.v. administration, the bioavailability by the oral route is calculated to be 44%. In vivo pharmacodynamic (PD) biomarker studies are therefore performed with this model. Following pharmacokinetic and tolerability studies, doses of AT7867 (90 mg/kg p.o. or 20 mg/kg i.p.) are administered to athymic mice bearing MES-SA tumors and the phosphorylation status of GSK3β and S6RP in tumors is monitored over time. Clear inhibition of phosphorylation of the two markers of pathway activity is seen at 2 and 6 hours following treatment with AT7867. By 24 hours, total levels of both GSK3β and S6RP are greatly reduced.
4-(4-氯苯基)-4-[4-(1H-吡唑-4-基)苯基]哌啶二盐酸盐 价格(试剂级)
更新日期 | 产品编号 | 产品名称 | CAS号 | 包装 | 价格 |
---|---|---|---|---|---|
2024-11-08 | HY-12059A | 1 mg | 545 | ||
2024-11-08 | HY-12059A | 4-(4-氯苯基)-4-[4-(1H-吡唑-4-基)苯基]哌啶二盐酸盐 | 1431697-86-7 | 5mg | 1200 |