GSK1059615

Catalog No.S1360 Batch:S136001

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Technical Data

Formula

C18H11N3O2S
Molecular Weight 333.36 CAS No. 958852-01-2
Solubility (25°C)* In vitro DMSO 2 mg/mL (5.99 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
0.1mg/ml Taking the 1 mL working solution as an example, add 50 μL of 2 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
Clear solution
5% DMSO 95% Corn oil
0.1mg/ml Taking the 1 mL working solution as an example, add 50 μL of 2 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <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.)

Preparing Stock Solutions

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.
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]
Features A novel, ATP-competitive, and reversible inhibitor of both PI3Kα, β, δ, and γ, and mTOR.

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 Assay:[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.

Customer Product Validation

, , Dr. Zhang of Tianjin Medical University

, , Antonino Maria Spartà from University of Bologn

, , Dr. Yong-Weon Yi from Georgetown University Medical Center

, , Saraswati Sukumar of Johns Hopkins University School of Medicine

Selleck's GSK1059615 has been cited by 15 publications

PIK-75 overcomes venetoclax resistance via blocking PI3K-AKT signaling and MCL-1 expression in mantle cell lymphoma [ Am J Cancer Res, 2022, 12(3):1102-1115] PubMed: 35411248
Phytochemicals inhibit migration of triple negative breast cancer cells by targeting kinase signaling. [ BMC Cancer, 2020, 20(1):4] PubMed: 31898540
Lethal Poisoning of Cancer Cells by Respiratory Chain Inhibition plus Dimethyl α-Ketoglutarate [ Cell Rep, 2019, 27(3):820-834] PubMed: 30995479
FRET biosensor-based kinase inhibitor screen for ERK and AKT activity reveals differential kinase dependencies for proliferation in TNBC cells. [ Biochem Pharmacol, 2019, 169:113640] PubMed: 31536726
[ ACS Pharmacol Transl Sci, 2019, ] PubMed: 32259061
Inhibition of RPTOR overcomes resistance to EGFR inhibition in triple-negative breast cancer cells [ Int J Oncol, 2018, 52(3):828-840] PubMed: 29344641
Development of a test that measures real-time HER2 signaling function in live breast cancer cell lines and primary cells. [Huang Y, et al. BMC Cancer, 2017, 17(1):199] PubMed: 28302091
Single and Combination Drug Screening with Aqueous Biphasic Tumor Spheroids [ SLAS Discov, 2017, 22(5):507-515] PubMed: 28324660
Gerosuppression by pan-mTOR inhibitors [ Aging (Albany NY), 2016, 8(12):3535-3551] PubMed: 28077803
Multiparametric Analysis of Oncology Drug Screening with Aqueous Two-Phase Tumor Spheroids. [ Mol Pharm, 2016, 13(11):3724-3735] PubMed: 27653969

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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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