AT7867

Catalog No.S1558

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.

Price Stock Quantity  
USD 420 In stock
USD 320 In stock
USD 970 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

AT7867 Chemical Structure

AT7867 Chemical Structure
Molecular Weight: 337.85

Validation & Quality Control

4 customer reviews :

Quality Control & MSDS

Related Compound Libraries

AT7867 is available in the following compound libraries:

Akt Inhibitors with Unique Features

  • Selective Akt Inhibitor

    CCT128930 AKT2-selective, IC50=6 nM.

  • Most Potent Akt Inhibitor

    AZD5363 Akt1, IC50=3 nM; Akt2, IC50=8 nM; Akt3, IC50=8 nM.

  • Akt Inhibitor in Clinical Trial

    Perifosine (KRX-0401) Phase III for relapsed and refractory multiple myeloma.

  • Newest Akt Inhibitor

    AZD5363 Potent inhibitor of all isoforms of Akt (Akt1/Akt2/Akt3) with IC50 of 3 nM/8 nM/8 nM, similar to P70S6K/PKA and lower activity towards ROCK1/2.

Product Information

  • Compare Akt Inhibitors
    Compare Akt Products
  • Research Area
  • Inhibition Profile

Product Description

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)

 View  More

IC50 17 nM 20 nM 32 nM 47 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]
Features

Protocol(Only for 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.
Formulation Formulated in a vehicle containing 10% DMSO, 20% water, and 70% hydroxypropyl-β-cyclodextrin (25% aqueous, w/v)
Dosages 20 mg/kg (i.p.) or 90 mg/kg (p.o.) once every 3 days
Administration Administered via i.p. or p.o.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Grimshaw KM, Mol Cancer Ther, 2010, 9(5), 1100-1110.

Chemical Information

Download AT7867 SDF
Molecular Weight (MW) 337.85
Formula

C20H20ClN3

CAS No. 857531-00-1
Storage 3 years -20℃powder
2 years -80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 68 mg/mL (201.27 mM)
Ethanol 5 mg/mL (14.79 mM)
Water <1 mg/mL
In vivo 15% Captisol, pH 9 10 mg/mL
* <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.
Chemical Name 4-(4-(1H-pyrazol-4-yl)phenyl)-4-(4-chlorophenyl)piperidine

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related Akt Products

  • Afuresertib (GSK2110183)

    Afuresertib (GSK2110183) is a potent, orally bioavailable Akt inhibitor with Ki of 0.08 nM, 2 nM, and 2.6 nM for Akt1, Akt2, and Akt3, respectively. Phase 2.

  • AT13148

    AT13148 is an oral, ATP-competitive, multi-AGC kinase inhibitor with IC50 of 38 nM/402 nM/50 nM, 8 nM, 3 nM, and 6 nM/4 nM for Akt1/2/3, p70S6K, PKA, and ROCKI/II, respectively. Phase 1.

  • SC79

    SC79 is a brain-penetrable Akt phosphorylation activator and an inhibitor of Akt-PH domain translocation.

  • MK-2206 2HCl

    MK-2206 2HCl is a highly selective inhibitor of Akt1/2/3 with IC50 of 8 nM/12 nM/65 nM in cell-free assays, respectively; no inhibitory activities against 250 other protein kinases observed. Phase 2.

    Features:The first allosteric small molecule inhibitor of Akt to enter clinical development.

  • AZD5363

    AZD5363 potently inhibits all isoforms of Akt(Akt1/Akt2/Akt3) with IC50 of 3 nM/8 nM/8 nM in cell-free assays, similar to P70S6K/PKA and lower activity towards ROCK1/2. Phase 2.

    Features:Moderate preclinical tolerability, and PD characteristics of an AKT inhibitor. Distinct profile from other AKT inhibitors in clinical development.

  • Ipatasertib (GDC-0068)

    Ipatasertib (GDC-0068) is a highly selective pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 5 nM/18 nM/8 nM in cell-free assays, 620-fold selectivity over PKA. Phase 2.

  • GSK690693

    GSK690693 is a pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 2 nM/13 nM/9 nM in cell-free assays, also sensitive to the AGC kinase family: PKA, PrkX and PKC isozymes. Phase 1.

  • Perifosine (KRX-0401)

    Perifosine (KRX-0401) is a novel Akt inhibitor with IC50 of 4.7 μM in MM.1S cells, targets pleckstrin homology domain of Akt. Phase 3.

  • A-674563

    A-674563 is an Akt1 inhibitor with Ki of 11 nM in cell-free assays, modest potent to PKA and >30-fold selective for Akt1 over PKC.

    Features:Orally bioavailable compound (achieved by replacing indole of A-443654 with phenyl moiety) and somewhat less selective for Akt over PKA than A-443654.

  • Triciribine

    Triciribine is a DNA synthesis inhibitor, also inhibits Akt in PC3 cell line and HIV-1 in CEM-SS, H9, H9IIIB, U1 cells with IC50 of 130 nM and 20 nM, respectively; does not inhibit PI3K/PDK1; 5000-fold less active in cells lacking adenosine kinase. Phase 1/2.

Recently Viewed Items

Tags: buy AT7867 | AT7867 supplier | purchase AT7867 | AT7867 cost | AT7867 manufacturer | order AT7867 | AT7867 distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Contact Us