For research use only. Not for therapeutic Use.
mTOR inhibitor-3 is a remarkably selective mTOR inhibitor with a Ki of 1.5 nM. mTOR inhibitor-3 suppresses mTORC1 and mTORC2 in cellular and in vivo pharmacokinetic (PK)/pharmacodynamic (PD) experiments.
mTOR inhibitor-3 (Compound 12i) inhibits mTOR with a Ki of 1.5 nM, 500-fold selectivity over closely related PI3 kinases. mTOR inhibitor-3 inhibits NCI-PC3 and MCF7neo/Her2 cells proliferation with IC50s of 150 nM and 57 nM, respectively[2].
mTOR inhibitor-3 (Compound 8h) has high free plasma clearance in both mice (1818 mL/min/kg) and rats (1538 mL/min/kg in rat) [1]. mTOR inhibitor-3 (Compounds 12i) is selected for this study due to its potency, selectivity, and favorable mouse PK profile. Plasma levels of mTOR inhibitor-3 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 inhibitor-3 has moderate terminal elimination half-life (t1/2=1.7 h for mouse(1 mg/kg, iv)). mTOR inhibitor-3 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].
| Catalog Number | I000773 |
| CAS Number | 1207358-59-5 |
| Synonyms | 1-ethyl-3-[4-[4-[(3S)-3-methylmorpholin-4-yl]-7-pyrimidin-2-yl-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-2-yl]phenyl]urea |
| Molecular Formula | C25H30N8O2 |
| Purity | ≥95% |
| InChI | InChI=1S/C25H30N8O2/c1-3-26-25(34)29-19-7-5-18(6-8-19)22-30-21-15-32(24-27-10-4-11-28-24)12-9-20(21)23(31-22)33-13-14-35-16-17(33)2/h4-8,10-11,17H,3,9,12-16H2,1-2H3,(H2,26,29,34)/t17-/m0/s1 |
| InChIKey | WQBAZXIQANTUOY-KRWDZBQOSA-N |
| SMILES | CCNC(=O)NC1=CC=C(C=C1)C2=NC3=C(CCN(C3)C4=NC=CC=N4)C(=N2)N5CCOCC5C |
| Reference | [1]. Pei Z, et al. Discovery and Biological Profiling of Potent and Selective mTOR Inhibitor GDC-0349. ACS Med Chem Lett. 2012 Nov 29;4(1):103-7. [2]. Koehler MF, et al. Potent, selective, and orally bioavailable inhibitors of the mammalian target of rapamycin kinase domain exhibiting single agent antiproliferative activity. J Med Chem. 2012 Dec 27;55(24):10958-71. |
