Afuresertib (GSK2110183)

Catalog No.S7521 Batch:S752101

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Technical Data

Formula

C18H17Cl2FN4OS
Molecular Weight 427.32 CAS No. 1047644-62-1
Solubility (25°C)* In vitro DMSO 85 mg/mL (198.91 mM)
Ethanol 85 mg/mL (198.91 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 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]
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 (from reference)

Kinase Assay:[1]
  • 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 Assay:[1]
  • 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.
Animal Study:[1]
  • Animal Models

    Female athymic nude and SCID mice bearing SKOV3 or BT474 tumors

  • Dosages

    100 mg/kg

  • Administration

    p.o.

Customer Product Validation

Data from [Data independently produced by , , ONCOLOGY LETTERS, 2018, https://doi.org/10.3892/ol.2018.8501]

Selleck's Afuresertib (GSK2110183) has been cited by 36 publications

Starvation-induced phosphorylation activates gasdermin A to initiate pyroptosis [ Cell Rep, 2024, 43(9):114728] PubMed: 39264808
p53 modulates kinase inhibitor resistance and lineage plasticity in NF1-related MPNSTs [ Oncogene, 2024, 43(19):1411-1430] PubMed: 38480916
SREBP1 deficiency diminishes glutamate-mediated HT22 cell damage and hippocampal neuronal pyroptosis induced by status epilepticus [ Heliyon, 2024, 10(1):e23945] PubMed: 38205297
TLR7/8 stress response drives histiocytosis in SLC29A3 disorders [ J Exp Med, 2023, 220(9)e20230054] PubMed: 37462944
TLR7/8 stress response drives histiocytosis in SLC29A3 disorders [ J Exp Med, 2023, 220(9)e20230054] PubMed: 37462944
Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells [ Cell Death Dis, 2023, 10.1038/s41419-023-06240-x] PubMed: 37938546
Azeliragon inhibits PAK1 and enhances the therapeutic efficacy of AKT inhibitors in pancreatic cancer [ Eur J Pharmacol, 2023, 948:175703] PubMed: 37028543
Biochemie der Myelomzelle bei Argininmangel und Canavanin-Supplementation [ DNB, 2023, ] PubMed: none
AKT constitutes a signal-promoted alternative exon-junction complex that regulates nonsense-mediated mRNA decay [ Mol Cell, 2022, S1097-2765(22)00480-4] PubMed: 35675814
PDGF-D-PDGFRβ signaling enhances IL-15-mediated human natural killer cell survival [ Proc Natl Acad Sci U S A, 2022, 119(3)e2114134119] PubMed: 35027451

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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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