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GSK1059615 PI3K inhibitor

Cat.No.S1360

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 PI3K inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 333.36

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Quality Control

Batch: S136001 DMSO]2 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Purity: 99.06%
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99.06

Solubility

In vitro
Batch:

DMSO : 2 mg/mL (5.99 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

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In vivo
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Chemical Information, Storage & Stability

Molecular Weight 333.36 Formula

C18H11N3O2S

 Storage (From the date of receipt)
CAS No. 958852-01-2 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles C1=CC2=NC=CC(=C2C=C1C=C3C(=O)NC(=O)S3)C4=CC=NC=C4

Mechanism of Action

Features
A novel, ATP-competitive, and reversible inhibitor of both PI3Kα, β, δ, and γ, and mTOR.
Targets/IC50/Ki
PI3Kα
(Cell-free assay)
0.4 nM
PI3Kβ
(Cell-free assay)
0.6 nM
PI3Kδ
(Cell-free assay)
2 nM
PI3Kγ
(Cell-free assay)
5 nM
mTOR
(Cell-free assay)
12 nM
In vitro
The pyridinylquinoline derivative GSK1059615 is a novel, ATP-competitive, and reversible inhibitor of the class I family of PI3Ks. This compound inhibits PI3K signaling, induces G1 arrest and apoptosis, especially in breast tumor cells. Data summarized in another review also shows that this inhibitor inhibits PI3Kα, β, γ and δ, with Ki of 0.42 nM, 0.6 nM, 0.47 nM and 1.7 nM, respectively. Another report shows that this chemical inhibits PI3Kα with IC50 of 2 nM. In T47D and BT474 cancer cells, it inhibits the phosphorylation of Akt at S473, with IC50 of 40 nM.
Kinase Assay
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. This compound 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 this chemical 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.
In vivo
In xenograft mice models of BT474 or HCC1954 breast cancer cells, GSK1059615 (25 mg/kg) effectively inhibits tumor growth.
References
  • [4] http://pubs.acs.org/doi/abs/10.1021/ml900028r

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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