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Purity: ≥98%
Miransertib (formerly known as ARQ 092) is an orally bioavailable and selective allosteric inhibitor of AKT with IC50 values of 5.0 nM, 4.5 nM, 16 nM for AKT1, 2,and 3, respectively. Patients with advanced solid tumors show a manageable safety profile. The PI3K/AKT signaling pathway may be inhibited as a result of ARQ 092's non-ATP-competitive binding to and inhibition of AKT activity. This may result in a decrease in tumor cell proliferation and the induction of tumor cell apoptosis. A human xenograft mouse model of endometrial adenocarcinoma showed reduced tumor growth when ARQ 092 was used as a potent inhibitor of the AKT1-E17K mutant protein.
| Targets |
Akt1 (IC50 = 2.7 nM); Akt3 (IC50 = 8.1 nM); Akt2 (IC50 = 14 nM); Leishmania; Akt1 E17K mutant
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| ln Vitro |
ARQ 092 blocks membrane translocation of inactive AKT and even dephosphorylates the membrane-associated active form, thereby perturbing AKT activity. Treatment with 50–500 nM ARQ 092 significantly inhibits neutrophil M2 integrin function and decreases platelet P-selectin exposure and Ib/IX/V-mediated agglutination. ARQ 092 inhibits proliferation in a wide variety of cancer cell lines, but it is most effective against leukemia, breast, endometrial, and colorectal cancer cell lines. Additionally, compared to cancer cell lines with wt-PIK3CA/PIK3R1 or PTEN mutations, ARQ 092 inhibition is more common in cancer cell lines containing PIK3CA/PIK3R1 mutations. In cells with mutations, ARQ 092 specifically targets the PI3K/AKT pathway and AKT and lowers GSK3 and GSK3 phosphorylation.
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| ln Vivo |
Short-term oral administration of ARQ 092 or hydroxyurea, a main therapy for sickle cell disease, diminishes heterotypic cell-cell interactions in venules of sickle cell disease mice challenged with TNF-α. ARQ 092 is well tolerated at a continuous daily dose of 60 mg or a dose of 600 mg when administered once a week, for several months. ARQ 092 is likely to inhibit the activity of all AKT isoforms in intravascular cells and thereby attenuates the process of thrombosis and inflammation in SCD patients. ARQ 092 is highly active in a subset of endometrial tumors that harbor PI3K pathway gene mutations.
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| Enzyme Assay |
Miransertib (ARQ-092) is an orally bioavailable, selective, and potent allostericAktinhibitor withIC50s of 2.7 nM, 14 nM and 8.1 nM forAkt1,Akt2,Akt3, respectively
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| Cell Assay |
Anti-proliferative cellular assays are conducted using the CellTiter Non-Radioactive Cell Proliferation Assay, which utilizes the production of formazan from a tetrazolium compound by live cells. The ATCC is where one can purchase AN3CA and A2780 cells. While A2780 cells are cultured in RPMI, AN3CA cells are cultured in DMEM. The test substance is applied to the cells in 96-well plates at a final DMSO concentration of no more than 0.5% v/v after they have been cultured for 24 hours and treated for 72 hours. Using MTS stock reagent (2 mg/mL in DPBS), PMS stock reagent (0.92 mg/mL in DPBS) is diluted 20 times before being diluted five times and added to each well of a 96-well plate.
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| Animal Protocol |
Mice：The experiments presented here employ only male offspring, and all mice are kept on outbred C57BL6/J backgrounds that have undergone more than 10 generations of backcrossing. Then, for the next four weeks, either the vehicle or Miransertib (100 mg/kg body weight) is given daily by oral gavage. When established hypertrophy was indicated at 12 weeks of age, administration started and lasted for 4 weeks until the mice were 16 weeks old. SHP2+/+ and SHP2Y279C/+ mice receive only vehicle treatment as controls.
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| References |
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| Molecular Formula |
C27H24N6
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|---|---|
| Molecular Weight |
432.5197
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| Exact Mass |
432.2062
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| Elemental Analysis |
C, 74.98; H, 5.59; N, 19.43
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| CAS # |
1313881-70-7
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| Related CAS # |
Miransertib hydrochloride;1313883-00-9
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| Appearance |
Solid powder
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| SMILES |
C1CC(C1)(C2=CC=C(C=C2)N3C4=C(C=CC(=N4)C5=CC=CC=C5)N=C3C6=C(N=CC=C6)N)N
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| InChi Key |
HNFMVVHMKGFCMB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H24N6/c28-24-21(8-4-17-30-24)25-32-23-14-13-22(18-6-2-1-3-7-18)31-26(23)33(25)20-11-9-19(10-12-20)27(29)15-5-16-27/h1-4,6-14,17H,5,15-16,29H2,(H2,28,30)
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| Chemical Name |
3-[3-[4-(1-aminocyclobutyl)phenyl]-5-phenylimidazo[4,5-b]pyridin-2-yl]pyridin-2-amine
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| Synonyms |
ARQ092; ARQ-092; ARQ 092
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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: ~86 mg/mL (~183.4 mM)
Water: <1 mg/mL Ethanol: ~6 mg/mL (~12.8 mM) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3120 mL | 11.5602 mL | 23.1203 mL | |
| 5 mM | 0.4624 mL | 2.3120 mL | 4.6241 mL | |
| 10 mM | 0.2312 mL | 1.1560 mL | 2.3120 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.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04980872 | Active Recruiting |
Drug: Miransertib | PROS/PS | Merck Sharp & Dohme LLC | November 2, 2021 | Phase 2 |
| NCT04316546 | Recruiting | Drug: MK-7075 (miransertib) |
Proteus Syndrome | National Human Genome Research Institute (NHGRI) |
May 20, 2022 | Phase 2 |
| NCT02594215 | Completed | Drug: MK-7075 (miransertib) |
Proteus Syndrome | ational Human Genome Research Institute (NHGRI) |
November 16, 2015 | Phase 1 |
ARQ 092 inhibits activation of neutrophils and platelets isolated from SCD patients in vitro.Haematologica.2017 Feb;102(2):246-259. |
Oral administration of ARQ 092 blocks AKT phosphorylation and activation of neutrophils and platelets isolated from SCD mice ex vivo.Haematologica.2017 Feb;102(2):246-259. |
(A–G). Oral administration of hydroxyurea and ARQ 092 has numerous beneficial effects in TNF-α-challenged SCD mice.Haematologica.2017 Feb;102(2):246-259. |
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