AT7867

Catalog No.S1558 Batch:S155803

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Technical Data

Formula

C20H20ClN3
Molecular Weight 337.85 CAS No. 857531-00-1
Solubility (25°C)* In vitro DMSO 68 mg/mL (201.27 mM)
Ethanol 5 mg/mL (14.79 mM)
Water Insoluble
* <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.)

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Biological Activity

Description AT7867 is a potent ATP-competitive inhibitor of Akt1/2/3 and p70S6K/PKA with IC50 of 32 nM/17 nM/47 nM and 85 nM/20 nM in cell-free assays, respectively; little activity outside the AGC kinase family.
Targets
Akt2 [1]
(Cell-free assay)		 PKA [1]
(Cell-free assay)		 Akt1 [1]
(Cell-free assay)		 Akt3 [1]
(Cell-free assay)		 p70 S6K [1]
(Cell-free assay)		 View More
17 nM 20 nM 32 nM 47 nM 85 nM
In vitro AT7867 also inhibits structurally related AGC kinases p70S6K and PKA with IC50 of 20 nM and 85 nM, respectively. AT7867 shows ATP-competitive activity to Akt2 with Ki of 18 nM. AT7867 exhibits antiproliferation in cell lines with PTEN or PIK3CA mutations and shows great potent to MES-SA, MDA-MB-468, MCF-7, HCT116 and HT29 with IC50 of 0.94 μM, 2.26 μM, 1.86 μM, 1.76 μM and 3.04 μM, respectively. AT7867 also suppresses the cell growth of U87MG, PC-3 and DU145 cells with IC50 of 8.22 μM, 10.37 μM and 11.86 μM, respectively. AT7867 suppresses Akt activity by inhibiting phosphorylation of GSK-3β in human tumor cells with IC50 of 2-4 μM. AT7867 also induces the phosphorylation of the following Akt direct substrates including proapoptotic transcription factors FKHR (FoxO1a), FKHRL1 (FoxO3a) and the downstream target S6RP in U87MG cells. [1]
In vivo AT7867 shows bioavailability of 44% in mice by p.o. route. AT7867 could increase the cleaved PARP in MES-SA xenografts at 20 mg/kg i.p. or 90 mg/kg p.o.. AT7867 significantly inhibits the tumor growth in MES-SA xenografts or U87MG xenografts with T/C of 0.37 and 0.51, respectively. [1]
Density 1.214 g/mL

Protocol (from reference)

Kinase Assay:[1]
  • In vitro kinase assays

    Kinase assays for Akt2, PKA, p70S6K, and CDK2/cyclin A are all carried out in a radiometric filter binding format. Assay reactions are set up in the presence of AT7867. For Akt2, the Akt2 enzyme and 25 μM Aktide-2T peptide (HARKRERTYSFGHHA) are incubated in 20 mM MOPS (pH 7.2), 25 mM β-glycerophosphate, 5 mM EDTA, 15 mM MgCl2, 1 mM sodium orthovanadate, 1 mM DTT, 10 μg/mL bovine serum albumin, and 30 μM ATP (1.16 Ci/mmol) for 4 hours. For PKA, the PKA enzyme and 50 μMpeptide (GRTGRRNSI) are incubated in 2 mM MOPS (pH 7.2), 25 mM β-glycerophosphate, 5 mM EDTA, 15 mM MgCl2, 1 mM orthovanadate, 1 mM DTT, and 40 μM ATP (0.88 Ci/mmol) for 20 minutes. For p70S6K, the p70S6K enzyme and 25 μMpeptide substrate (AKRRRLSSLRA) are incubated in 10 mM MOPS (pH 7), 0.2 mM EDTA, 1 mM MgCl2, 0.01% β-mercaptoethanol, 0.1 mg/mL bovine serum albumin, 0.001% Brij-35, 0.5% glycerol, and 15 μM ATP (2.3 Ci/mmol) for 60 min. For CDK2, the CDK2/cyclin A enzyme and 0.12 μg/mL histone H1 are incubated in 20 mM MOPS (pH 7.2), 25 mM β-glycerophosphate, 5 mM EDTA, 15 mM MgCl2, 1 mM sodium orthovanadate, 1 mM DTT, 0.1 mg/mL bovine serum albumin, and 45 μM ATP (0.78 Ci/mmol) for 4 hours. Assay reactions are stopped by adding an excess of orthophosphoric acid, and the stopped reaction mixture is then transferred to Millipore MAPH filter plates and filtered. The plates are then washed, scintillant is added, and radioactivity is measured by scintillation counting on a Packard TopCount. IC50 values are calculated from replicate curves using GraphPad Prism software. Akt1 and Akt3 enzyme assays are carried out.
Cell Assay:[1]
  • Cell lines

    MES-SA, MDA-MB-468, MCF-7, HCT116, HT29, U87MG, PC-3 and DU145 cells

  • Concentrations

    0-100 μM , dissolved to a 10 mM stock in DMSO

  • Incubation Time

    72 hours

  • Method

    Cells are plated in 96-well microplates at 5 × 103 per well in medium supplemented with 10% fetal bovine serum and grown for 24 hours before treatment with AT7867. AT7867 or vehicle control is added to the cells for 72 hours. Following this, Alamar Blue solution is added. The IC50 value for AT7868 is calculated in GraphPad Prism using nonlinear regression analysis and a sigmoidal dose-response (variable slope) equation.
Animal Study:[1]
  • Animal Models

    Human MES-SA uterine sarcoma cells or U87MG human glioblastoma cells are injected s.c. in the right flank of BALB/c mice.

  • Dosages

    20 mg/kg (i.p.) or 90 mg/kg (p.o.) once every 3 days

  • Administration

    Administered via i.p. or p.o.

Customer Product Validation

, , Mark Axelrod of University Of Virginia

, , Mark Axelrod of University Of Virginia

, , Dr. Zhang of Tianjin Medical University

, , Mark Axelrod of University Of Virginia

Selleck's AT7867 has been cited by 25 publications

Functional restoration of lysosomes and mitochondria through modulation of AKT activity ameliorates senescence [ Exp Gerontol, 2023, 173:112091] PubMed: 36657533
Inhibition of IκB Kinase Is a Potential Therapeutic Strategy to Circumvent Resistance to Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer Cells [ Cancers (Basel), 2022, 14(21)5215] PubMed: 36358633
Dual Inhibition of AKT and MEK Pathways Potentiates the Anti-Cancer Effect of Gefitinib in Triple-Negative Breast Cancer Cells [ Cancers (Basel), 2021, 13(6)1205] PubMed: 33801977
Combined Omics Approaches Reveal the Roles of Non-canonical WNT7B Signaling and YY1 in the Proliferation of Human Pancreatic Progenitor Cells [ Cell Chem Biol, 2020, S2451-9456(20)30340-8] PubMed: 33125912
Genipin, a natural AKT inhibitor, targets the PH domain to affect downstream signaling and alleviates inflammation [ Biochem Pharmacol, 2019, 170:113660] PubMed: 31605673
A natural AKT inhibitor swertiamarin targets AKT-PH domain, inhibits downstream signaling, and alleviates inflammation. [ FEBS J, 2019, 10.1111/febs.15112] PubMed: 31665825
Inhibitors of AKT kinase increase LDL receptor mRNA expression by two different mechanisms [ PLoS One, 2019, 14(6):e0218537] PubMed: 31216345
The flavonoid baicalin improves glucose metabolism by targeting the PH domain of AKT and activating AKT/GSK3β phosphorylation. [ FEBS Lett, 2019, 593(2):175-186] PubMed: 30489635
Shengui Sansheng San extraction is an angiogenic switch via regulations of AKT/mTOR, ERK1/2 and Notch1 signal pathways after ischemic stroke [Liu B, et al. Phytomedicine, 2018, 44:20-31] PubMed: 29895489
Src-mediated regulation of the PI3K pathway in advanced papillary and anaplastic thyroid cancer. [ Oncogenesis, 2018, 7(2):23] PubMed: 29487290

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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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