GSK1059615

Catalog No.S1360

For research use only.

GSK1059615 is a dual inhibitor of PI3Kα/β/δ/γ (reversible) and mTOR with IC50 of 0.4 nM/0.6 nM/2 nM/5 nM and 12 nM, respectively. Phase 1.

GSK1059615 Chemical Structure

CAS No. 958852-01-2

Selleck's GSK1059615 has been cited by 13 publications

Purity & Quality Control

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Biological Activity

Description GSK1059615 is a dual inhibitor of PI3Kα/β/δ/γ (reversible) and mTOR with IC50 of 0.4 nM/0.6 nM/2 nM/5 nM and 12 nM, respectively. Phase 1.
Features A novel, ATP-competitive, and reversible inhibitor of both PI3Kα, β, δ, and γ, and mTOR.
Targets
PI3Kα [1]
(Cell-free assay)
PI3Kβ [1]
(Cell-free assay)
PI3Kδ [1]
(Cell-free assay)
PI3Kγ [1]
(Cell-free assay)
mTOR [1]
(Cell-free assay)
0.4 nM 0.6 nM 2 nM 5 nM 12 nM
In vitro

The pyridinylquinoline derivative GSK1059615 is a novel, ATP-competitive, and reversible inhibitor of the class I family of PI3Ks. GSK1059615 inhibits PI3K signaling, induces G1 arrest and apoptosis, especially in breast tumor cells. [2] Data summarized in another review also shows that GSK1059615 inhibits PI3Kα, β, γ and δ, with Ki of 0.42 nM, 0.6 nM, 0.47 nM and 1.7 nM, respectively. [3] Another report shows that GSK1059615 inhibits PI3Kα with IC50 of 2 nM. In T47D and BT474 cancer cells, GSK1059615 inhibits the phosphorylation of Akt at S473, with IC50 of 40 nM. [4]

In vivo In xenograft mice models of BT474 or HCC1954 breast cancer cells, GSK1059615 (25 mg/kg) effectively inhibits tumor growth. [3]

Protocol (from reference)

Kinase Assay:[4]
  • HTRF In vitro Profiling Assays for PI3K Inhibition:

    The measurement of the GSK1059615-dependent inhibition of the PI3Ks is accessed using a HTRF based PI3K profiling assay kit. 400 pM enzyme is used in PI3Kα and δ assays, 200 pM in PI3Kβ assays, and 1 nM in PI3Kγ assay. In addition, the PI3Kα, β, and δ assays are run with 150 mM NaCl and 100 μM ATP, while the PI3Kγ assay is run with no NaCl and 15 μM ATP. All reactions are run at 10 μM PIP2. GSK1059615 is serially diluted (3-fold in DMSO), and 50 nL is transferred to a 384-well low-volume assay plate. PI3K Reaction Buffer is prepared by diluting the stock 1:4 with de-ionized water. Freshly prepared DTT is added at a final concentration of 5 mM on the day of use. Enzyme addition and GSK1059615 pre-incubation are initiated by the addition of 2.5 µL of PI3K in reaction buffer. Plates are incubated at room temperature for 15 min. Reactions are initiated by addition of 2.5 µL of 2× substrate solution (PIP2 and ATP in 1× reaction buffer). Plates are incubated at room temperature for one hour. Reactions are quenched by the addition of 2.5 µL of stop solution. The quenched reactions are then processed to detect product formation by adding 2.5 µL of Detection Solution. Following a 1-hour incubation in the dark, the HTRF signal is measured on the Envision plate reader set for 330nm excitation and dual emission detection at 620nm (Eu) and 665nm (APC). The IC50 value is then obtained.

Cell Research:[4]
  • Cell lines: T47D and BT474 cells
  • Concentrations: 0–1 μM, serially diluted (3-fold) in DMSO
  • Incubation Time: 30 min
  • Method: Cells are plate at a density of 1 × 104 cells per well in clear flat-bottomed 96-well plates and incubated overnight. Then, GSK1059615 is added and the plates are incubated for 30 min. At the end of incubation, media is aspirated from the plates, and the plate is wash once with cold PBS. 80 μL MSD Lysis buffer is added into each well and the plates are incubated on a shaker at 4 °C for at least 30 min. For Akt duplex assay, plates are washed with 200 μL/well wash buffer for 4 times and tapped on paper towel to blot. Then, 60 μL lysates is added to each well and the plates are incubated on shaker at room temperature for 1 hour. After another 4 times washing, antibody is added (25 μL per well) and the plates are incubated on shaker for 1 hour and washed again. Finally, Read Buffer is added (150 μL per well) and the plates are read immediately. IC50 values are then obtained.

Solubility (25°C)

In vitro

DMSO 2 mg/mL
(5.99 mM)
Water Insoluble
Ethanol Insoluble

Chemical Information

Molecular Weight 333.36
Formula

C18H11N3O2S

CAS No. 958852-01-2
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1=CC2=NC=CC(=C2C=C1C=C3C(=O)NC(=O)S3)C4=CC=NC=C4

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00695448 Terminated Drug: GSK1059615 Solid Tumours GlaxoSmithKline June 24 2008 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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

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