T133

T133 is an orally active ATP-competitive mTOR inhibitor with an IC50 of 0.34 nM and a Ki of 0.17 nM. It effectively inhibits the phosphorylation of AKT, S6K1, and 4EBP1. T133 suppresses the proliferation and migration of cancer cells, inducing apoptosis, cell cycle arrest, and autophagy. It demonstrates dose-dependent antitumor efficacy in xenograft mouse models. T133 is applicable in cancer research, including gastric and lung cancers.

T133 (Compound 51) effectively inhibits recombinant mTOR kinase activity with an IC50 of 0.34 nM and a Ki of 0.17 nM. It demonstrates over 10 times selectivity for mTOR compared to most class I PI3K isoforms, with Ki values of 1.8 nM for PI3Kδ, 4.9 nM for PI3Kγ, 47 nM for PI3Kα, and 125 nM for PI3Kβ. T133 significantly inhibits the proliferation of HGC-27, NCI-H1299, and T-47D cancer cells with IC50 values of 0.82 μM, 1.22 μM, and 0.28 μM, respectively, over 72 hours. Additionally, it markedly inhibits the migration of HGC-27 gastric cancer cells at concentrations of 1-2.5 μM within 16 hours. T133 exhibits a dose-dependent inhibition of the PI3K/AKT/mTOR signaling pathway and induces apoptosis in HGC-27, NCI-H1299, and T-47D cancer cells between 0.3-100 μM over 2-24 hours. Furthermore, it prompts autophagy in HGC-27 gastric cancer cells at 20-100 nM after 48 hours and arrests these cells in the G1 phase of the cell cycle at concentrations of 100-500 nM after 24 hours.

T133 (Compound 51), administered orally at doses of 30-60 mg/kg once daily, achieved 83% and 92% tumor growth inhibition in the HGC-27 gastric cancer xenograft model over 18 days, while maintaining a favorable safety profile. Similarly, T133 administered in the same manner for 26 days effectively inhibited tumor growth in the NCI-H1299 non-small cell lung cancer xenograft model, also demonstrating a good safety profile.