1. PI3K/Akt/mTOR
    Protein Tyrosine Kinase/RTK
    Stem Cell/Wnt
  2. Akt
    PKA

Afuresertib (Synonyms: GSK2110183)

Cat. No.: HY-15727 Purity: 98.91% ee.: 99.70%
Data Sheet SDS Handling Instructions

Afuresertib is an orally available, ATP-competitive, pan-AKT inhibitor with Ki of 0.08, 2 and 2.6 nM against AKT1, AKT2 and AKT3, respectively.

For research use only. We do not sell to patients.
Afuresertib Chemical Structure

Afuresertib Chemical Structure

CAS No. : 1047644-62-1

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $77 In-stock
5 mg $70 In-stock
10 mg $95 In-stock
50 mg $270 In-stock
100 mg $470 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Other Forms of Afuresertib:

    Afuresertib purchased from MCE. Usage Cited in: J Physiol. 2017 Jul 1;595(13):4207-4225.

    Effects of pharmacological inhibitors on AngII-mediated activation of L-type Ca2+ channels in NVCMs. NVCMs are treated with vehicle, Erlotinib, H-89, Afuresertib (1 μM), Gö6983, CID755673, KN-93, SCH772984, Bosutinib or Quinalizarin for 30 min before treatment of AngII.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    Afuresertib is an orally available, ATP-competitive, pan-AKT inhibitor with Ki of 0.08, 2 and 2.6 nM against AKT1, AKT2 and AKT3, respectively.

    IC50 & Target

    Ki: 0.08 nM (AKT1), 2 nM (AKT2), 2.6 nM (AKT3)[1]
    IC50: 0.2 nM (AKT1E17K), 1.3 nM (PKA), 0.9 nM (PKG1α), 4 nM (PKG1β)[1]

    In Vitro

    Afuresertib (GSK2110183) shows concentration-dependent effect on multiple AKT substrate phosphorylation levels, including GSK3β, PRAS40, FOXO and Caspase 9 in both BT474 and LNCaP cell lines. GSK2110183 consistently has potent anti-proliferative effects on a variety of hematological malignancies. Overall 65% of the hematological cell lines are sensitive to GSK2110183 (EC50<1 µM). Among solid tumor cell lines, 21% have EC50<1 µM in response to GSK2110183[1].

    In Vivo

    Mice bearing BT474 breast tumor xenografts are dosed orally with either vehicle or GSK2110183 at 10, 30 or 100 mg/kg daily for 21 days which results in 8, 37 and 61% tumor growth inhibition (TGI), respectively. Mice tolerates GSK2110183 well, with 1-3% body weight loss reported after 5 days of dosing which recovers over the course of the study. Other tumor xenograft models which possess an activation of the AKT pathway are explored to further demonstrate compound efficacy. Mice bearing SKOV3 ovarian tumor xenografts with 10, 20 and 30 mg/kg GSK2141795 QD displays a 73, 85 or 93% TGI, respectively, compared to vehicle control. Similarly, mice treated with GSK2110183 at 10, 30 and 100 mg/kg results in 23, 37 and 97% TGI, respectively, of SKOV3 xenografts[1].

    Clinical Trial
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    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 2.3402 mL 11.7008 mL 23.4017 mL
    5 mM 0.4680 mL 2.3402 mL 4.6803 mL
    10 mM 0.2340 mL 1.1701 mL 2.3402 mL
    Please refer to the solubility information to select the appropriate solvent.
    Kinase Assay
    [1]

    The potency of compounds against AKT enzymes is measured. Since Afuresertib (GSK2110183) and GSK2141795 are highly potent inhibitors of the 3 isoforms of AKT, the true potency (Ki) of the inhibitors is initially determined at low enzyme concentrations (0.1 nM AKT1, 0.7 nM AKT2, and 0.2 nM AKT3) using a filter binding assay and then confirmed with progress curve analysis. In the filter binding assay, a pre-mix of enzyme plus inhibitor is incubated for 1 h and then added to a GSKα peptide (Ac-KKGGRARTSSFAEPG-amide) and [γ33P] ATP. Reactions are terminated after 2 h and the radio labeled AKT peptide product is captured in a phospho-cellulose filter plate. Progress curve analysis utilized continuous real-time fluorescence detection of product formation using the Sox-AKT-tide substrate (Ac-ARKRERAYSF-d-Pro-Sox-Gly-NH2). GSK2110183 and GSK2141795 are tested against a diverse panel of kinase assays at GlaxoSmithKline and Millipore. Initially, the compounds are tested at 0.5 and 10 µM in all available kinase assays and are followed up with full IC50 curves against a subset of enzymes that showed strong inhibition against 0.5 µM, for which in-house assay are not available[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [1]

    Afuresertib (GSK2110183) is dissolved in DMSO (10 mM) and stored, and then diluted with appropriate media before use[1].

    BT474 and LNCaP cell lines are typically grown in RPMI 160 medium containing 10% FBS. Some cell lines are grown in media specified by the vendor. A 3-day proliferation assay using CellTiter-Glo (CTG) is performed to measure the growth inhibition by the compounds (e.g., Afuresertib) at 0-30 µM. Cell growth is determined relative to untreated (DMSO) controls. EC50's are calculated from inhibition curves using a 4- or 6-parameter fitting algorithm in the Assay Client application[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    Afuresertib (GSK2110183) is formulated in 20% polyethylene glycol (PEG) 400/1% DMSO (Mice)[1].

    Mice[1]
    Tumors are initiated by injecting either cells (SKOV3, CAPAN-2 and HPAC) or a tumor fragments (BT474) subcutaneously into 6-8 week female athymic nude (SKOV3) and SCID (all others) mice. Once tumors reached between 120 and 300 mm3, mice are randomized according to tumor volume into groups of n=7-10 mice per treatment. GSK2110183 and GSK2141795 are administered daily at various doses by oral gavage. In combination experiments, GSK1120212 is also administered daily by oral gavage. Tumor volumes and body weight are measured twice weekly, tumor volume is measured with calipers and calculated using equation: Tumor volume (mm3)=(length×width)2/2. Results are represented as percent inhibition on completion of dosing=100×[1-average growth of drug-treated population/average growth of vehicle-treated control population]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    427.32

    Formula

    C₁₈H₁₇Cl₂FN₄OS

    CAS No.

    1047644-62-1

    Storage

    -20°C, protect from light, stored under nitrogen

    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    DMSO: ≥ 40 mg/mL

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

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    Inquiry Information

    Product Name:
    Afuresertib
    Cat. No.:
    HY-15727
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