MTI-31

Product NameMTI-31
CAS1567915-38-1
MFC26H30N6O3
MW474.55
EINECS
MOL File1567915-38-1.mol

Chemical Properties

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

Usage And Synthesis

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.

IC 50

mTOR: 0.2 nM (Ki); mTOR: 39 nM (IC₅₀, 100 μM ATP); mTORC1; mTORC2

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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