ARQ-092 is an orally bioavailable, selective, and potent allosteric Akt inhibitor with IC50 of 2.7 nM, 14 nM and 8.1 nM for Akt1, Akt2, Akt3, respectively.
Miransertib 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Caov3
1 μmol/l
2 hours
Evaluate the combined effect of ARQ 092 and ARQ 087, results showed only inhibition of pS6
Anticancer Drugs. 2017 Jun;28(5):503-513.
IGROV-1
1 μmol/l
72 hours
Evaluate the combined effect of ARQ 092 and ARQ 087, results showed no changes in cell cycle and apoptosis
Anticancer Drugs. 2017 Jun;28(5):503-513.
AN3CA
1 μmol/l
72 hours
Evaluate the combined effect of ARQ 092 and ARQ 087, results showed G1 phase cell cycle arrest and increased apoptosis
Anticancer Drugs. 2017 Jun;28(5):503-513.
BC-3
1.5 µM
24 h
Both miransertib and MK-4440 reduced the number of live BC-3 cells and decreased the phosphorylation levels of Akt, but had a minimal effect on the phosphorylation of downstream targets.
Front Oncol. 2021 Jun 18;11:670275.
BJAB
1.06 µM
72 h
Both miransertib and MK-4440 reduced the number of live BJAB cells and decreased the phosphorylation levels of Akt, but had a minimal effect on the phosphorylation of downstream targets.
Front Oncol. 2021 Jun 18;11:670275.
FL-18
1 µM and 5 µM
72 h
Both miransertib and MK-4440 reduced the number of live FL-18 cells and decreased the phosphorylation levels of Akt and its downstream targets such as FOXO1, S6K, and S6.
Front Oncol. 2021 Jun 18;11:670275.
Pik3caH1047R ECs
2 µM
24 h
To assess the impact of miransertib on the PI3K/AKT signaling pathway, results showed that miransertib significantly reduced p-Akt and p-Pras40 levels and regulated the expression of Ang2 and cell cycle regulators.
EMBO Mol Med. 2022 Jul 7;14(7):e15619.
HUVEC-vPK cells
1 µM
24 h
Inhibition of AKT phosphorylation, leading to Caspase-3 cleavage and induction of apoptosis
Cell Death Dis. 2023 Oct 18;14(10):688.
Miransertib 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
FL-18 xenograft model
Oral
100 mg/kg
Once daily for three weeks
Miransertib alone or in combination with sirolimus significantly reduced tumor growth in the FL-18 xenograft model.
Front Oncol. 2021 Jun 18;11:670275.
Mice
PIK3CA-related capillary venous malformation mouse model
Oral
30 mg/kg
Once daily, continuous treatment
Miransertib showed some efficacy in treating PIK3CA-related capillary venous malformation in mice, slightly reducing venous malformation volumes and extending lifespan, but it did not significantly impact platelet levels, anemia, or histological abnormalities.
Signal Transduct Target Ther. 2024 Jun 17;9(1):146
Mice
Pik3caH1047R mutant mouse model
Intraperitoneal injection
75 mg/kg and 35 mg/kg
Administered at P1 and P2 days, continued until P6 days
To evaluate the preventive and therapeutic effects of miransertib on PI3K-driven vascular malformations, results showed that miransertib effectively prevented and induced the regression of vascular malformations and inhibited the PI3K signaling pathway.
EMBO Mol Med. 2022 Jul 7;14(7):e15619.
C57BL/6 mice
Myocardial ischemia-reperfusion injury model
Intraperitoneal injection
120 mg/kg
Single dose 1 hour before surgery
To investigate the protective effect of Miransertib on myocardial ischemia-reperfusion injury, results showed that Miransertib reversed the alleviating autophagy effect of Metformin by inhibiting the Akt signaling pathway
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