| Identification | Back Directory | [Name]
MTI-31 | [CAS]
1567915-38-1 | [Synonyms]
MTI-31
LXI-15029
Benzamide, N-methyl-3-[2-[(3S)-3-methyl-4-morpholinyl]-4-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)pyrido[2,3-d]pyrimidin-7-yl]-
mTOR kinase inhibitor,tissue factor,mTORC2,mTOR inhibitor,Inhibitor,EGFR mutant cancer,mTOR-TF axis,Mammalian target of Rapamycin,apoptosis,MTI 31,mTOR,inhibit,MTI31,mTORC1,lipid metabolism,tumor microenvironment | [Molecular Formula]
C26H30N6O3 | [MOL File]
1567915-38-1.mol | [Molecular Weight]
474.55 |
| Chemical Properties | Back Directory | [density ]
1.275±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 8.33 mg/mL (17.55 mM; ultrasonic and warming and heat to 60°C) | [form ]
Solid | [pka]
14.45±0.46(Predicted) | [color ]
White to yellow |
| Hazard Information | Back Directory | [Uses]
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]. | [in vivo]
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]. | Animal Model: | Female nude mice bearing tumors of MDA-MB-453, 786-O or HCC1806[1] | | Dosage: | 2.5, 5, 10, 20, 40 mg/kg for MDA-MB-453 and 786-O; 20 and 40 mg/kg for HCC1806 | | Administration: | Treated orally via a once daily (qd) regimen | | Result: | 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.
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| [IC 50]
mTOR: 0.2 nM (Ki); mTOR: 39 nM (IC50, 100 μM ATP); mTORC1; mTORC2 | [storage]
Store at -20°C | [References]
[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. DOI:10.1158/1078-0432.CCR-18-2548
[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. DOI:10.18632/oncotarget.11490
[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. DOI:10.1016/j.jconrel.2019.11.005 |
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