For research use only. Not for therapeutic Use.
MTI-31 (LXI-15029) is a potent, orally active and highly selective inhibitor of mTORC1 and mTORC2. MTI-31 is selective for mTOR (Kd: 0.20 nM) versus PIK3CA, PIK3CB and PIK3G with >5,000 fold selectivity in mTOR binding assays. MTI-31 shows an IC50 of 39 nM for mTOR in LANCE assay of mTOR substrate phosphorylation with 100 μM ATP. MTI-31 can be used for the research of breast cancer[1].
MTI-31 acts as a potent and selective inhibitor of mTOR enzymatic activity capable of targeting both mTORC1 and mTORC2 functions in cancer cells[1].
MTI-31 (0.01-100 μM) elicits a potent and more substantial inhibition of cell growth than that of Rapamycin[1].
Treatment with MTI-31 for 6 h demonstrates a dose-dependent inhibition of both the mTORC1 substrates P-S6K1(T389), P-S6(S235/6), P-4EBP1(T70) and mTORC2 substrate P-AKT(S473), achieving 50% inhibition at ≤0.12 μM in three representative tumor cell lines harboring mTOR pathway dysregulation (786-O renal, U87MG glioma and MDA-MB-453 breast)[1].
MTI-31-induced apoptosis requires mTORC2-regulated Bim- and GSK3 activity[1].
MTI-31 is a potent mTOR inhibitor in vivo and elicits strong antitumor efficacy. MTI-31(5-40 mg/kg; orally) is efficacious in several tumor models harboring HER2+/PIK3CAmut and/or PTEN-deficiency exemplified by MDA-MB-453 and 786-O[1].
Treatment of tumor bearing nude mice with orally administered MTI-31 inhibits growth of H1975 tumors (25 mg/kg/d; orally) or U87MG tumors (30 mg/kg/d; orally)[2].
| Catalog Number | I032847 |
| CAS Number | 1567915-38-1 |
| Synonyms | N-methyl-3-[2-[(3S)-3-methylmorpholin-4-yl]-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrido[2,3-d]pyrimidin-7-yl]benzamide |
| Molecular Formula | C26H30N6O3 |
| Purity | ≥95% |
| InChI | InChI=1S/C26H30N6O3/c1-16-13-34-11-10-31(16)26-29-23-21(24(30-26)32-19-6-7-20(32)15-35-14-19)8-9-22(28-23)17-4-3-5-18(12-17)25(33)27-2/h3-5,8-9,12,16,19-20H,6-7,10-11,13-15H2,1-2H3,(H,27,33)/t16-,19?,20?/m0/s1 |
| InChIKey | LVPBYQVQBZLDAU-DZIBYMRMSA-N |
| SMILES | CC1COCCN1C2=NC3=C(C=CC(=N3)C4=CC(=CC=C4)C(=O)NC)C(=N2)N5C6CCC5COC6 |
| Reference | [1]. Zhang Q, et, al. A Novel mTORC1/2 Inhibitor (MTI-31) Inhibits Tumor Growth, Epithelial-Mesenchymal Transition, Metastases, and Improves Antitumor Immunity in Preclinical Models of Lung Cancer. Clin Cancer Res. 2019 Jun 15;25(12):3630-3642. [2]. Qian J, et, al. Molecular regulation of apoptotic machinery and lipid metabolism by mTORC1/mTORC2 dual inhibitors in preclinical models of HER2+/PIK3CAmut breast cancer. Oncotarget. 2016 Oct 11;7(41):67071-67086. [3]. Wang X, et, al. Non-immunogenic, low-toxicity and effective glioma targeting MTI-31 liposomes . J Control Release. 2019 Dec 28;316:381-392. |
