| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
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| Targets |
mTOR 0.2 nM (Ki) mTOR 39 nM (IC50, 100 μM ATP) mTORC1 mTORC2
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|---|---|
| ln Vitro |
MTI-31 targets both mTORC1 and mTORC2 activities in cancer cells by acting as a strong and specific inhibitor of mTOR enzymatic activity[1]. MTI-31 (0.01-100 μM) inhibits cell growth more strongly and significantly than Rapamycin[1]. The mTORC1 substrates P-S6K1(T389), P-S6(S235/6), P-4EBP1(T70), and the mTORC2 substrate P-AKT(S473) show dose-dependent inhibition upon 6 hours of treatment with MTI-31. In three representative tumor cell lines harboring mTOR pathway dysregulation (786-O renal, U87MG glioma, and MDA-MB-453 breast)], 50% inhibition was achieved at ≤0.12 μM. Bim- and GSK3 activity must be mTORC2-regulated for MTI-31-induced apoptosis to occur[1].
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| ln Vivo |
MTI-31 exhibits substantial anticancer efficaciousness and is a potent mTOR inhibitor in vivo. MTI-31 (5–40 mg/kg; oral) is effective in a number of tumor models that have PTEN deficit and/or HER2+/PIK3CAmut, as demonstrated by MDA-MB-453 and 786-O[1]. MTI-31 given orally to tumor-bearing nude mice suppresses the growth of H1975 tumors (25 mg/kg/d; oral) and U87MG tumors (30 mg/kg/d; oral)[2].
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: MDA-MB-453 cells Tested Concentrations: 0.01, 0.1, 1, 10, 100 μM Incubation Duration: 3 days Experimental Results: Dramatically inhibited cellular proliferation after treatment for 3 days. Western Blot Analysis[1] Cell Types: 786-O renal, U87MG glioma and MDA-MB-453 breast cells Tested Concentrations: 0.12, 0.37, 1.11, 3.33, 10 μM Incubation Duration: 6 hrs (hours) Experimental Results: Demonstrated 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). |
| Animal Protocol |
Animal/Disease Models: Female nude mice bearing tumors of MDA-MB-453, 786-O or HCC1806[1]
Doses: 2.5, 5, 10, 20, 40 mg/kg for MDA-MB-453 and 786- O; 20 and 40 mg/kg for HCC1806 Route of Administration: Treated orally via a one time/day (qd) regimen Experimental Results: Was efficacious in several tumor models harboring HER2+/PIK3CAmut and/or PTEN-deficiency exemplified by MDA-MB-453 and 786- O. Demonstrated a dose proportional tumor growth inhibition (TGI) with a minimum efficacious dose (MED) of 5 mg/kg (>50% TGI, p<0.01) and a maximum tolerated dose (MTD) of 40 mg/kg (7 -15% body weight loss without mortality). In contrast, had limited efficacy in the HER2-/PIK3CAwt HCC1806 breast tumor model even at the highest 40 mg/kg. |
| References |
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| Additional Infomation |
mTORC 1/2 Inhibitor LXI-15029 is an orally bioavailable inhibitor of raptor-mammalian target of rapamycin (mTOR) complex 1 (mTOR complex 1; mTORC1) and rictor-mTOR complex 2 (mTOR complex 2; mTORC2), with potential antineoplastic activity. Upon oral administration, mTORC1/2 inhibitor LXI-15029 binds to the kinase domain of mTOR and inhibits both mTORC1 and mTORC2, in an ATP-competitive manner. This inhibits mTOR-mediated signaling and leads to both an induction of apoptosis and a decrease in the proliferation of mTORC1/2-expressing tumor cells. mTOR is a serine/threonine kinase that is upregulated in certain tumor cell types. It plays an important role in the PI3K/Akt/mTOR signaling pathway, which is often deregulated in cancer cells and promotes cell growth, survival, and resistance to chemotherapy and radiotherapy.
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| Molecular Formula |
C26H30N6O3
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|---|---|
| Molecular Weight |
474.554805278778
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| Exact Mass |
474.237
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| CAS # |
1567915-38-1
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| PubChem CID |
118591386
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| Appearance |
White to yellow solid powder
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| LogP |
3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
35
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| Complexity |
745
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O1CC2CCC(C1)N2C1C2C=CC(C3C=CC=C(C(NC)=O)C=3)=NC=2N=C(N2CCOC[C@@H]2C)N=1
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| InChi Key |
LVPBYQVQBZLDAU-DZIBYMRMSA-N
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| InChi Code |
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
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| Chemical Name |
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
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 8.33 mg/mL (17.55 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.83 mg/mL (1.75 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1073 mL | 10.5363 mL | 21.0726 mL | |
| 5 mM | 0.4215 mL | 2.1073 mL | 4.2145 mL | |
| 10 mM | 0.2107 mL | 1.0536 mL | 2.1073 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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