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GSK1059615

GSK1059615

Manufacturer	Selleckchem
Category	Oncology Inhibitors & Compound Libraries Small Molecules By Organ Breast Cancer
Type	Inhibitors
Specific against	other
Amount	10 mg
Item no.	S1360-10
Targets	PI3K, MTOR
CASRN	958852-01-2
eClass 6.1	30220300
eClass 9.0	32160605
Available
Alias	958852-01-2'
Administration	Oral gavage
Animal Models	Xenograft mice models of BT474 or HCC1954 cells
Cell lines	T47D and BT474 cells
Chemical Name	(Z)-5-((4-(pyridin-4-yl)quinolin-6-yl)methylene)thiazolidine-2, 4-dione
Clinical Trials	A Phase I clinical trial for GSK1059615 for solid tumors has been terminated.
Concentrations	0–1 uM, serially diluted (3-fold) in DMSO
Description	GSK1059615 is a novel and dual inhibitor of PI3Kalpha, PI3Kbeta, PI3Kdelta, PI3Kgamma and mTOR with IC50 of 0.4 nM, 0.6 nM, 2 nM, 5 nM and 12 nM, respectively.
Dosages	25 mg/kg
Features	GSK1059615 is a novel, ATP-competitive, and reversible inhibitor of both PI3Kalpha, beta, delta, and gamma, and mTOR.
IC50	0.4 nM, 0.4 nM, 0.4 nM, 0.4 nM, 0.4 nM, 0.4 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 PI3Kalpha, beta, gamma and delta, with Ki of 0.42 nM, 0.6 nM, 0.47 nM and 1.7 nM, respectively. [3] Another report shows that GSK1059615 inhibits PI3Kalpha 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]
Incubation Time	30 min
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 PI3Kalpha and delta assays, 200 pM in PI3Kbeta assays, and 1 nM in PI3Kgamma assay. In addition, the PI3Kalpha, beta, and delta assays are run with 150 mM NaCl and 100 uM ATP, while the PI3Kgamma assay is run with no NaCl and 15 uM ATP. All reactions are run at 10 uM 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 uL of PI3K in reaction buffer. Plates are incubated at room temperature for 15 min. Reactions are initiated by addition of 2.5 uL 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 uL of stop solution. The quenched reactions are then processed to detect product formation by adding 2.5 uL 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.
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 uL 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 uL/well wash buffer for 4 times and tapped on paper towel to blot. Then, 60 uL 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 uL per well) and the plates are incubated on shaker for 1 hour and washed again. Finally, Read Buffer is added (150 uL per well) and the plates are read immediately. IC50 values are then obtained.
Molecular Weight (MW)	333, 36
Picture ChemicalStructure Description	GSK1059615 Chemical Structure
Picture Description 1	, , Saraswati Sukumar of Johns Hopkins University School of Medicine, GSK1059615purchased from Selleck, We treated all of drugs in T47D which has a PI3KCA H1044R mutation with the concentration shown below for 1 hour and performed western blot analysis using antibodies to phospho-AKT(SERINE 472), and total AKT.
Picture Description 2	, , Dr Zhang of Tianjin Medical University, GSK1059615purchased from Selleck, Breast cancer cells were pretreated with 100ng/ml EGF for 15 min and then treated with the indicated concentrations of GSK1059615 for 24 hours.
Solubility (25C)	DMSO 2 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL
Storage	2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO

Note: The presented information and documents (Manual, Product Datasheet, Safety Datasheet and Certificate of Analysis) correspond to our latest update and should serve for orientational purpose only. We do not guarantee the topicality. We would kindly ask you to make a request for specific requirements, if necessary.

All products are intended for research use only (RUO). Not for human, veterinary or therapeutic use.

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Amount: 10 mg

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