Miransertib (ARQ 092) HCl

Catalog No.S8339 Batch:S833902

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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 40%PEG300 5%Tween80 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. 
Clear solution
5% DMSO 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. 
* <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

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

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 14 publications

The Combination of Afatinib With Dasatinib or Miransertib Results in Synergistic Growth Inhibition of Stomach Cancer Cells [ World J Oncol, 2024, 15(2):192-208] PubMed: 38545471
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

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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.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.