| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
mTOR 0.2 nM (Ki) mTOR 39 nM (IC50, 100 μM ATP) mTORC1 mTORC2
mTOR (mammalian target of rapamycin). MTI-31 is a potent, orally active, and highly selective inhibitor of mTORC1 and mTORC2. |
|---|---|
| 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].
MTI-31 is a potent inhibitor of mTOR with a Kd of 0.2 nM in binding assays. It displays >5,000-fold selectivity over PIK3CA, PIK3CB, and PIK3G. As a highly selective mTOR inhibitor, it blocks the phosphorylation and activation of downstream targets of mTORC1 (such as S6K1 and 4E-BP1) and mTORC2 (such as AKT at Ser473). MTI-31 is orally active and has been shown to be effective against various tumor models. |
| 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].
In vivo, MTI-31 is effective against various tumor models, including those with HER2+/PIK3CAmut and/or PTEN deficiency, when administered orally. As an mTOR inhibitor, it blocks mTORC1 and mTORC2 signaling, leading to reduced tumor growth and increased apoptosis. |
| Enzyme Assay |
In vitro kinase assays for MTI-31 are performed to evaluate its binding affinity for mTOR and its selectivity over other kinases. mTOR binding affinity is measured using binding assays, and IC50 or Kd values are calculated. Selectivity profiling is performed against a panel of kinases, including PIK3CA, PIK3CB, and PIK3G.
|
| 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). In vitro cell-based assays are conducted to evaluate the effects of MTI-31 on mTOR signaling and cell viability. Cells are treated with MTI-31, and the phosphorylation of mTORC1 targets (S6K1, 4E-BP1) and mTORC2 targets (AKT Ser473) is measured by Western blotting. Cell viability and proliferation are assessed using standard assays such as MTT or CCK-8. |
| 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. In vivo animal studies with MTI-31 are conducted in tumor xenograft models. The compound is typically administered orally. Its effects on tumor growth, survival, and biomarkers of mTOR signaling are assessed in various tumor models, including those with HER2+/PIK3CAmut and/or PTEN deficiency. |
| ADME/Pharmacokinetics |
MTI-31 is an orally active compound. Detailed pharmacokinetic parameters such as half-life, bioavailability, and tissue distribution are not extensively documented in publicly available literature.
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| Toxicity/Toxicokinetics |
No specific toxicity data are publicly available for MTI-31. As an mTOR inhibitor, its toxicity profile would be expected to be related to its mechanism of action. Standard safety assessments would be required for any therapeutic development.
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| References |
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| Additional Infomation |
LXI-15029, an mTORC 1/2 inhibitor, is an orally bioavailable inhibitor of mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) with potential antitumor activity. After oral administration, LXI-15029 binds to the kinase domain of mTOR, competitively inhibiting mTORC1 and mTORC2. This inhibits the mTOR-mediated signaling pathway, leading to reduced apoptosis and proliferation in mTORC1/2-expressing tumor cells. mTOR is a serine/threonine kinase that is upregulated in certain tumor cell types. It plays a crucial role in the PI3K/Akt/mTOR signaling pathway, which is frequently dysregulated in cancer cells and promotes cell growth, survival, and resistance to chemotherapy and radiotherapy.
MTI-31 (LXI-15029) is a potent, orally active, and highly selective inhibitor of mTORC1 and mTORC2 with a Kd of 0.2 nM for mTOR and >5,000-fold selectivity over PI3K isoforms. It is effective against various tumor models and is a valuable research tool for studying mTOR signaling in cancer. The compound is not approved for human therapeutic use and is strictly for research purposes. |
| Molecular Formula |
C26H30N6O3
|
|---|---|
| Molecular Weight |
474.554805278778
|
| 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
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
35
|
| Complexity |
745
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
O1CC2CCC(C1)N2C1C2C=CC(C3C=CC=C(C(NC)=O)C=3)=NC=2N=C(N2CCOC[C@@H]2C)N=1
|
| 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
|
| 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.
Link: https://clinicaltrials.gov/ct2/show/NCT03125746
Conditions:Advanced Breast CancerProducts are for research use only; We do not sell to patients
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