| 包装 | 价格(元) |
| 1mg | 电议 |
| 5mg | 电议 |
Animal experiment: | Mice, Rats and Dogs[1]Female nu/nu mice are dosed with the GNE-477 HCl salt as a solution intraveinously (1 mg/kg) in 5% DMSO/5% cremophor and dosed orally as a solution in 80% PEG (5 mg/kg). Male rats are dosed with the GNE-477 TFA salt as a solution intraveinously (1 mg/kg) in 5% DMSO/5% cremophor and dosed orally as a solution in 80% PEG (5 mg/kg). Male beagle dogs are dosed with the GNE-477 HCl salt as a solution intraveinously (1 mg/kg) in 10% HP-β-CD and dosed orally as a suspension in MCT (2 mg/kg). Efficacy study of GNE-477 in the PC3-NCI tumor xenograft model is proformed. The percent of tumor growth inhibition (TGI) at the end of study (day 14) is measured and compared with the vehicle control group. |
| 产品描述 | IC50: 4 and 21 nmol/L for PI3K and mTOR, respectively GNE-477 is a potent dual PI3K/mTOR inhibitor. Owing to the common association with oncogenic malignancies, the PI3K/AKT/mTOR signaling pathway is regarded as an attractive area of research for the identification of oral small molecule inhibitors. In vitro: GNE-477 was found to inhibit PI3K-α, β, δ, and γ with IC50s of 4, 86, 6, and 15 nM, respectively. [1]. In vivo: A direct comparison of GNE-477 with its des-methyl analog revealed that the trend of reduced in vivo clearance in rats is also observed in dogs and mice. The clearance improvement was significant in dogs where the des-methyl analog was cleared at two-thirds the rate of hepatic blood flow while GNE-477 had low clearance. In an study evaluating the tumor growth inhibition of a PC3 tumor xenograft10 over 14 days, stasis was achieved at a 20 mg/kg QD dose of GNE-477 and significant inhibition was found with doses as low as 1 mg/kg QD. GNE-477 was generally well tolerated during this study as shown by acceptable levels of weight loss comparable to that in the vehicle cohort [1]. Clinical trial: N/A Reference: |
m.cnreagent.com