tcsc1383 mTOR-IN-1

mTOR-IN-1 is a remarkably selective mTOR inhibitor with a K_i of 1.5 nM. mTOR-IN-1 suppresses mTORC1 and mTORC2 in cellular and in vivo pharmacokinetic (PK)/pharmacodynamic (PD) experiments.

IC50 & Target: Ki: 1.5 nM (mTOR)^[1]


mTORC1, mTORC2^[1]

In Vitro: mTOR-IN-1 (Compound 12i) inhibits mTOR with a K_i of 1.5 nM, 500-fold selectivity over closely related PI3 kinases. mTOR-IN-1 inhibits NCI-PC3 and MCF7neo/Her2 cells proliferation with IC₅₀s of 150 nM and 57 nM, respectively^[2].

In Vivo: mTOR-IN-1 (Compound 8h) has high free plasma clearance in both mice (1818 mL/min/kg) and rats (1538 mL/min/kg in rat) ^[1]. mTOR-IN-1 (Compounds 12i) is selected for this study due to its potency, selectivity, and favorable mouse PK profile. Plasma levels of mTOR-IN-1 6 h following oral administration in PC3 tumor-bearing mice along with the fold decreases of phosphorylated mTORC1 and -2 substrates relative to time-matched vehicle controls. mTOR-IN-1 has moderate terminal elimination half-life (t_1/2=1.7 h for mouse(1 mg/kg, iv)). mTOR-IN-1 achieves tumor stasis at the highest 200 mg/kg/day dose examined, which appears to also be approaching the limit of tolerability for this molecule^[2].