Cat No:LP000196
Product Name:AZD2014
CAS No:1009298-59-2
Purity: ≥99%
Solubility: In DMSO
Storage: -10°C
The inhibitory effects of AZD2014 are measured against isolated recombinant mTOR enzyme (IC50 of 2.81 nM) as well as in cellular assays measuring both mTORC1 and mTORC2 activities. In MDAMB468 cells, AZD2014 decreases the phosphorylation of the mTORC1 substrate ribosomal protein S6 (Ser235/236) with a mean IC50 value of 210 nM and the mTORC2 substrate AKT (Ser473) with a mean IC50 value of 78 nM[1].
AZD2014 induces dose-dependent tumor growth inhibition in several xenograft and primary explant models. The antitumor activity of AZD2014 is associated with modulation of both mTORC1 and mTORC2 substrates, consistent with its mechanism of action. The pharmacokinetics of AZD2014 in mice is tested upon administration of doses between 7.5 and 15 mg/kg. A dose-dependent increase in Cmax and AUC is observed following single dose and repeat dosing of AZD2014: Cmax range from 1 to 16 μM and AUC range from 220 to 5,042 μM·h across this dose range. The pharmacodynamic effect of AZD2014 against an mTORC1 biomarker (phosphorylation of S6) and an mTORC2 biomarker (phosphorylation of AKT) is assessed in SCID mice bearing MCF7 xenografts following administration of 3.75, 7.5, and 15 mg/kg AZD2014. There is a good relationship between the drug plasma concentrations and biomarker levels (estimated p-AKT IC50 of 0.119 μM total, 53% SE, and estimated p-S6 IC50 0.392 μM, 28.8% SE)[1].
