1. PI3K/Akt/mTOR
  2. Akt

ARQ-092 

Cat. No.: HY-19719 Purity: 98.07%
Data Sheet SDS Handling Instructions

ARQ-092 is an orally bioavailable, selective, and potent allosteric Akt inhibitor with IC50s of 2.7 nM, 14 nM and 8.1 nM for Akt1, Akt2, Akt3, respectively.

For research use only. We do not sell to patients.
ARQ-092 Chemical Structure

ARQ-092 Chemical Structure

CAS No. : 1313881-70-7

Size Price Stock Quantity
10 mM * 1 mL in DMSO $114 In-stock
1 mg $80 In-stock
5 mg $120 In-stock
10 mg $210 In-stock
50 mg $910 In-stock
100 mg $1700 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

ARQ-092 is an orally bioavailable, selective, and potent allosteric Akt inhibitor with IC50s of 2.7 nM, 14 nM and 8.1 nM for Akt1, Akt2, Akt3, respectively.

IC50 & Target

IC50: 2.7 nM (Akt1), 14 nM (Akt2), 8.1 nM (Akt3)[1]

In Vitro

ARQ-092 (Compound 21a) demonstrates high enzymatic potency against Akt1, Akt2 and Akt3, as well as potent cellular inhibition of Akt activation and the phosphorylation of the downstream target PRAS40. ARQ-092 shows strong affinity for un-phosphorylated fulllength Akt1 and potently inhibited the phosphorylated form of full-length Akt isoforms. In a large panel of cell lines derived from various tumor types, ARQ-092 shows potent anti-proliferative activity in cell lines containing PIK3CA/PIK3R1 mutations compared to those with wild-type (wt) PIK3CA/PIK3R1 or PTEN loss. ARQ-092 shows excellent inhibition of p-Akt (S473) and p-Akt (T308) in both AN3CA and A2780 cells. The inhibition of the downstream protein p-PRAS40 (T246) is observed with ARQ-092 (IC50=0.31 μM)[1].

In Vivo

In a mouse pharmacokinetic study, (po at 100 mg/kg, iv at 5 mg/kg), ARQ-092 (Compound 21a) shows an oral bioavailability of 23%. ARQ-092 results in 99%, 95% and 58% reductions in p-Akt (S473), p-Akt (T306) and p-PRAS40 (T246), respectively, after tumor-bearing mice are treated with 100 mg/kg po. The inhibition of phosphorylation is sustained at eight hours. The plasma concentration of ARQ-092 at one hour is 2.1 μM and decreased to 0.26 μM at 8 hours, while in the tumor, the concentration is 21.0 μM at one hour and 9.6 μM at 8 hours[1]. To determine the effects of ARQ-092 on cardiac function, echocardiographic analysis of SHP2+/+ and SHP2Y279C/+ littermates is conducted, either in the presence of orally administered vehicle or ARQ-092 (100 mg/kg/day), at 12, 14, and 16 weeks of age. By 12 weeks of age, SHP2Y279C/+ mice show significant left ventricular hypertrophy, as indicated by decreased chamber dimension and increased posterior wall thickness compared with those of littermate controls; hypertrophy in these mice continued to progress over the 4 week time period. Treatment of the SHP2Y279C/+ mice with ARQ-092 normalizes the hypertrophic cardiomyopathy (HCM) phenotype as early as 2 weeks following treatment, with levels comparable to those in SHP2+/+ at this time point[2].

Clinical Trial
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References
Preparing Stock Solutions
Concentration Volume Mass 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
Please refer to the solubility information to select the appropriate solvent.
Cell Assay
[1]

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. AN3CA and A2780 cells are obtained from the ATCC. AN3CA cells are cultured in DMEM, and A2780 cells are cultured in RPMI supplemented with 10% FBS, 100 units/mL Penicillin, 100 μg/mL Streptomycin, and 2 mM Glutamine at 37 °C under 5% CO2. Cells are plated in 96-well plates at 2,000-10,000 cells/well, cultured for 24 h, and treated with the test compound for 72 h at a final DMSO concentration no greater than 0.5% v/v. PMS stock reagent (0.92 mg/mL in DPBS) is diluted 20-fold in MTS stock reagent (2 mg/mL in DPBS), and this MTS/PMS mixture is diluted 5-fold into each well of the 96-well plate. The plates are incubated for 3-4 h, and the absorbance of formazan is measured at 490 nm. The data are normalized to the untreated controls, the dose-response curves are fit to a four-parameter logistic equation, and the IC50 values are determined. All IC50 values reported are the geometric mean of at least two independent determinations[1].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

ARQ-092 is dissolved in 0.01 M phosphoric acid (vehicle) at a concentration of 20 mg/mL and filter sterilized[2].

Mice[2]
SHP2Y279C/+ mice are used. Only male progeny are used for the experiments herein and all mice are maintained on outbred C57BL6/J backgrounds, backcrossed for more than 10 generations. Either vehicle or ARQ-092 (100 mg/kg body weight) is then daily administered by oral gavage for 4 weeks. Administration began at 12 weeks of age (after established hypertrophy is indicated), and continued for 4 weeks, until the mice reach 16 weeks of age. As controls, SHP2+/+ and SHP2Y279C/+ mice are treated with vehicle alone.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

432.52

Formula

C₂₇H₂₄N₆

CAS No.

1313881-70-7

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 40.2 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 98.07%

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Product Name:
ARQ-092
Cat. No.:
HY-19719
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