Afuresertib (GSK2110183)

For research use only.

Catalog No.S7521

17 publications

Afuresertib (GSK2110183) Chemical Structure

CAS No. 1047644-62-1

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.

Selleck's Afuresertib (GSK2110183) has been cited by 17 publications

1 Customer Review

  • Analysis of the mechanism of action of the enhanced anti‑tumor effect of the combination therapy of suboptimal doses of pomalidomide plus dexamethasone and afuresertib in MM cells. (A‑C) The altered expression of protein substrates was analyzed in two MM cell lines that were treated with suboptimal doses of PD, or AFU, or the PD and AFU combination. The XG‑7 and U266 cell lines were subjected to the indicated treatments for 48 and 72 h, respectively. (A) Caspases, (B) substrates related mainly to the working mechanism of IMiDs, (C) substrates mainly related to the working mechanism of afuresertib, and (D) two primary MM cell cultures, were subjected to the analysis in the same manner as the two MM cell lines. In the expression panel of p‑FoxO3a/FoxO1, the upper band represents p‑FoxO3a and the lower band represents p‑FOXO1. PD, pomalidomide plus dexamethasone; AFU, Afuresertib; MM, multiple myeloma; IMiDs, immunomodulatory drugs.

    ONCOLOGY LETTERS, 2018, https://doi.org/10.3892/ol.2018.8501. Afuresertib (GSK2110183) purchased from Selleck.

Purity & Quality Control

Choose Selective Akt Inhibitors

Biological Activity

Description 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.
Targets
Akt1 [1]
(Cell-free assay)
Akt2 [1]
(Cell-free assay)
Akt3 [1]
(Cell-free assay)
0.08 nM(Ki) 2 nM(Ki) 2.6 nM(Ki)
In vitro

Afuresertib inhibits the kinase activity of the E17K AKT1 mutant protein with EC50 of 0.2 nM. Afuresertib shows a concentration-dependent effect on multiple AKT substrate phosphorylation levels, including GSK3b, PRAS40, FOXO and Caspase 9. Overall 65% of the hematological cell lines are sensitive to afuresertib (EC50 < 1 μM). Among tested solid tumor cell lines, 21% have EC50 < 1 μM in response to afuresertib.[1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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SW1417 MmXQS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NYfncmtnPzJiaILz MlfGS5Jwf3SqIHnubIljcXSrb36gc4YhcHWvYX6gV3cyPDF5IHPlcIx{KGG2IEG6NVAhdW:uYYKgdoF1cW9ib3[gZ49ueG:3bnSgbY4heHKnc3XuZ4Uhd2ZiTj37N{1cOy2leXPsc5Bzd3C7bD21MUgzNW[udX;yc{01NWmxZH:tdIhmdnmuYX3pco8qNTZuOD3kbY1mfGi7bD2gNkw1NDdvdILpc5hwNTNuNDy2MFcufGW2cnHofYRzdy1{SD3wfZJq\G:dNDyzMYReeHm{aX3p[IlvNTFveXzddIhmdnmufXHj[ZRidWmmZTDpcoN2[mG2ZXSg[o9zKDd{IHjyd{whUUN3MDC9JFAvODNizszNMi=> NIK4W|E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzOjF7NEKyM{c,S2iHTVLMQE9iRg>?
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COR-L23 MWfHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M1LSfFczKGi{cx?= M33xOGdzd3e2aDDpcohq[mm2aX;uJI9nKGi3bXHuJGNQWi2OMkOgZ4VtdHNiaX7jeYJifGWmIH\vdkA4OiCqcoOgZpkhS2WubD30bZRmei2JbH:gdoVi\2WwdDDiZZNm\CCjc4PhfUwhUUN3MDC9JFUvOzd|IN88UU4> MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNlE6PDJ{Lze+R4hGVUKOPD;hQi=>
A549 M3:xdmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MlLTO|IhcHK| MWfHdo94fGhiaX7obYJqfGmxbjDv[kBpfW2jbjDBOVQ6KGOnbHzzJIlv[3WkYYTl[EBnd3JiN{KgbJJ{KGK7IFPlcIwufGm2ZYKtS4xwKHKnYXflcpQh[mG|ZXSgZZN{[XluIFnDOVAhRSB3Lkm5N{DPxE1w MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNlE6PDJ{Lze+R4hGVUKOPD;hQi=>
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NCI-H1792 MnfXS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M1XI[VczKGi{cx?= NFXVZ2lIem:5dHigbY5pcWKrdHnvckBw\iCqdX3hckBPS0lvSEG3PVIh[2WubIOgbY5kfWKjdHXkJIZweiB5MjDodpMh[nliQ3XscE11cXSncj3HcI8hemWjZ3XueEBj[XOnZDDhd5NigSxiSVO1NEA:KDdwM{C3JO69VS5? MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNlE6PDJ{Lze+R4hGVUKOPD;hQi=>
SW1463 NVe0dY9ST3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NIfiWng4OiCqcoO= NELJcW1Iem:5dHigbY5pcWKrdHnvckBw\iCqdX3hckBUXzF2NkOgZ4VtdHNiaX7jeYJifGWmIH\vdkA4OiCqcoOgZpkhS2WubD30bZRmei2JbH:gdoVi\2WwdDDiZZNm\CCjc4PhfUwhUUN3MDC9JFkvPzJ3IN88UU4> MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyNlE6PDJ{Lze+R4hGVUKOPD;hQi=>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-GSK3 / GSK3 / p-PRAS40 / PRAS40 / p-FOXO / p-Casp9 / p-AKT / AKT / p-MEK / p-ERK / Erk ; 

PubMed: 24978597     


BT474 (left) and LNCaP (right) cell lines were treated with DMSO or GSK2110183 for 1 h. Western analysis was performed to assay levels of phosphorylated and total GSK-3, PRAS40, AKT and ERK, phosphorylated Foxo, Caspase 9, and MEK. Tubulin was used as a loading control. 

ATG3 / ATG12 / LC3B ; 

PubMed: 30867818     


Alterations in autophagy-related proteins induced by AKT inhibition.

24978597 30867818
In vivo Mice bearing BT474 breast tumor xenografts are dosed with afuresertib (p.o.) at 10, 30 or 100 mg/kg daily which results in 8, 37 and 61% TGI, respectively. Mice bearing SKOV3 ovarian tumor xenografts are treated with 10, 30 and 100 mg/kg afuresertib which results in 23, 37 and 97% TGI, respectively.[1]

Protocol

Kinase Assay:[1]
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Potency (Ki*) of afuresertib:

The true potency (Ki*) of the inhibitor 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-KKGGRARTSS-FAEPG-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 utilizes continuous real-time fluorescence detection of product formation using the Sox-AKT-tide substrate (Ac-ARKRERAYSF-d-Pro-Sox-Gly-NH2).
Cell Research:[1]
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  • Cell lines: Hematological cell lines and solid tumor cell lines
  • Concentrations: 30 μM
  • Incubation Time: 72 h
  • Method: A 3-day proliferation assay using CellTiter-Glo is performed to measure the growth inhibition by the compounds 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.
    (Only for Reference)
Animal Research:[1]
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  • Animal Models: Female athymic nude and SCID mice bearing SKOV3 or BT474 tumors
  • Dosages: 100 mg/kg
  • Administration: p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 85 mg/mL (198.91 mM)
Ethanol 85 mg/mL (198.91 mM)
Water 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 Information

Molecular Weight 427.32
Formula

C18H17Cl2FN4OS

CAS No. 1047644-62-1
Storage powder
in solvent
Synonyms N/A
Smiles CN1C(=C(C=N1)Cl)C2=C(SC(=C2)C(=O)NC(CC3=CC(=CC=C3)F)CN)Cl

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Dosage mg/kg Average weight of animals g Dosing volume per animal ul Number of animals
Step 2: Enter the in vivo formulation ()
% DMSO % % Tween 80 % ddH2O
CalculateReset

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and SDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04374630 Recruiting Drug: Paclitaxel|Drug: Afuresertib Platinum-resistant Ovarian Cancer Laekna Limited June 9 2020 Phase 2
NCT04060394 Recruiting Drug: Phase I and Phase II: LAE001/prednisone + afuresertib Metastatic Castration-resistant Prostate Cancer Laekna Limited September 13 2019 Phase 1|Phase 2
NCT02235740 Terminated Drug: Afuresertib|Drug: Carfilzomib Cancer Novartis|Amgen November 2014 Phase 1
NCT02240212 Completed Drug: Afuresertib|Drug: Paclitaxel Cancer Novartis Pharmaceuticals|Novartis October 2014 Phase 1
NCT02177682 Terminated Drug: Afuresertib Neoplasms Haematologic Novartis Pharmaceuticals|Novartis August 13 2014 Phase 1

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.

Handling Instructions

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

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

  • * Indicates a Required Field

Akt Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID