Miransertib (ARQ 092) HCl

Catalog No.S8339 Batch:S833902

Technical Data

Formula

C₂₇H₂₅ClN₆

Molecular Weight

468.98

CAS No.

1313883-00-9

Solubility (25°C)*

In vitro

DMSO

75 mg/mL (159.92 mM)

Ethanol

4 mg/mL (8.52 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution	5% DMSO 1 95% Corn oil	0.31mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 6.2 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	1.25mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 25 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

Miransertib (ARQ 092) HCl is a novel, orally bioavailable and selective AKT pathway inhibitor exhibiting a manageable safety profile among patients with advanced solid tumors.

Targets

Akt2 ^[1] (Cell-free assay)	Akt1 ^[1] (Cell-free assay)	Akt3 ^[1] (Cell-free assay)
4.5 nM	5 nM	16 nM

In 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 blocks αMβ2 integrin function in neutrophils and reduces P-selectin exposure and glycoprotein Ib/IX/V-mediated agglutination in platelets^[2]. In a large panel of diverse cancer cell lines, ARQ 092 inhibits proliferation across multiple tumor types but are most potent in leukemia, breast, endometrial, and colorectal cancer cell lines. Moreover, inhibition by ARQ 092 is more prevalent in cancer cell lines containing PIK3CA/PIK3R1 mutations compared to those with wt-PIK3CA/PIK3R1 or PTEN mutations^[1]. ARQ 092 targets the PI3K/AKT pathway and AKT specifically and reduces phosphorylation of GSK3α and GSK3β in mutation-positive cells^[3].

In 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^[2]. ARQ 092 is highly active in a subset of endometrial tumors that harbor PI3K pathway gene mutations^[1].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines MDA-MB-453 cells; NCI-H1650 cells; KU-19-19 cells Concentrations 0, 0.012, 0.037, 0.11, 0.33, and 1 μM Incubation Time 2 h Method Cells (MDA-MB-453: 1.5×10⁶; NCI-H1650: 1×10⁶; KU-19-19: 0.7×10⁶) are plated into 6 well plates, left overnight, and then treated with full media containing different concentrations (0, 0.012, 0.037, 0.11, 0.33, and 1 μM) of AKT inhibitors (ARQ 092, ARQ 751, MK-2206, GDC-0068) for 2 hours. Cells are treated under designated conditions and lysates are extracted. Proteins are resolved from extracts using SDS-PAGE followed by immunoblotting.
Animal Study:^{^[2]}	Animal Models Male SCD mice Dosages 100 mg/10ml/kg Administration oral administration

Cell Assay:^{^[1]}

Cell lines
MDA-MB-453 cells; NCI-H1650 cells; KU-19-19 cells
Concentrations
0, 0.012, 0.037, 0.11, 0.33, and 1 μM
Incubation Time
2 h
Method
Cells (MDA-MB-453: 1.5×10⁶; NCI-H1650: 1×10⁶; KU-19-19: 0.7×10⁶) are plated into 6 well plates, left overnight, and then treated with full media containing different concentrations (0, 0.012, 0.037, 0.11, 0.33, and 1 μM) of AKT inhibitors (ARQ 092, ARQ 751, MK-2206, GDC-0068) for 2 hours. Cells are treated under designated conditions and lysates are extracted. Proteins are resolved from extracts using SDS-PAGE followed by immunoblotting.

Animal Study:^{^[2]}

Animal Models
Male SCD mice
Dosages
100 mg/10ml/kg
Administration
oral administration

References

Customer Product Validation

: Data from [Data independently produced by , , Neurobiol Dis, 2018, pii: S0969-9961(18)30149-9]

Selleck's Miransertib (ARQ 092) HCl has been cited by 13 publications

Insights into the Conformational Plasticity of the Protein Kinase Akt1 by Multi-Lateral Dipolar Spectroscopy [ Chemistry, 2023, e202203959.]	PubMed: 36795969
AKT mutant allele-specific activation dictates pharmacologic sensitivities [ Nat Commun, 2022, 13(1):2111]	PubMed: 35440569
Cilia-Mediated Insulin/Akt and ST2/JNK Signaling Pathways Regulate the Recovery of Muscle Injury [ Adv Sci (Weinh), 2022, e2202632]	PubMed: 36373718
Revisiting the Resazurin-Based Sensing of Cellular Viability: Widening the Application Horizon [ Biosensors (Basel), 2022, 12(4)196]	PubMed: 35448256
Viability fingerprint of glioblastoma cell lines: roles of mitotic, proliferative, and epigenetic targets [ Sci Rep, 2021, 11(1):20338]	PubMed: 34645858
1,3-dichloro-2-propanol induced hepatic lipid accumulation by inhibiting autophagy via AKT/mTOR/FOXO1 pathway in mice [ Food Chem Toxicol, 2021, 157:112578]	PubMed: 34560177
Metformin suppresses inflammation and apoptosis of myocardiocytes by inhibiting autophagy in a model of ischemia-reperfusion injury [ Int J Biol Sci, 2020, 16(14):2559-2579]	PubMed: 32792857
FGF20-FGFR1 signaling through MAPK and PI3K controls sensory progenitor differentiation in the organ of Corti [ Dev Dyn, 2020, 10.1002/dvdy.231]	PubMed: 32735383
Preclinical Efficacy of Covalent-Allosteric AKT Inhibitor Borussertib in Combination with Trametinib in KRAS-Mutant Pancreatic and Colorectal Cancer. [ Cancer Res, 2019, 79(9):2367-2378]	PubMed: 30858154
PI3K/AKT inhibitors aggravate death receptor-mediated hepatocyte apoptosis and liver injury. [ Toxicol Appl Pharmacol, 2019, 381:114729]	PubMed: 31445927

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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