| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
GSK1059615 is a novel, potent and reversible inhibitor of P13K (phosphatidylinositol-3-kinases) with potential anticancer activity. It is an analog of pyridinylquinoline that also inhibits PI3Kα oncogenic mutants. It functions as a dual inhibitor of PI3Kα/β/δ/γ and mTOR with IC50 values of 0.4 nM, 0.6 nM, 2.5 nM, and 12 nM, respectively. Within the ATP-binding pocket, the thiazolidinedione ring of GSK1059615 interacts with the catalytic lysine (Lys833). GSK-1059615 is said to cause G1 arrest and apoptosis in a number of cell lines when used in cellular assays. The breast tumor cells stand out among them as being more sensitive. Additionally, in xenograft mice, GSK1059615 significantly reduces tumor growth and raises plasma insulin levels.
| Targets |
PI3Kα (IC50 = 0.4 nM); PI3Kβ (IC50 = 0.6 nM); PI3Kγ (IC50 = 2 nM); PI3Kδ (IC50 = 5 nM); mTOR (IC50 = 12 nM)
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| ln Vitro |
GSK1059615 inhibits PI3Kα, β, γ and δ, with Ki of 0.42 nM, 0.6 nM, 0.47 nM and 1.7 nM, respectively[1]. GSK1059615 inhibits the phosphorylation of Akt at S473 in T47D and BT474 cancer cells with an IC50 of 40 nM[2].
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| ln Vivo |
GSK1059615 (25 mg/kg) effectively inhibits tumor growth in xenograft mice models of BT474 or HCC1954 breast cancer cells[1].
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| Enzyme Assay |
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. The PI3Kα, β, and δ assay is carried out with no NaCl and 15 μM ATP, whereas the PI3Kγ assays are performed with 150 mM NaCl and 100 μM ATP. At 10 M PIP2, all reactions are carried out. A 50 nL sample of GSK1059615 is transferred to a 384-well low-volume assay plate after being serially diluted (3-fold in DMSO). De-ionized water is diluted 1:4 with the stock to create the PI3K Reaction Buffer. On the day of use, freshly prepared DTT is added at a final concentration of 5 mM. 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 330 nm excitation and dual emission detection at 620 nm (Eu) and 665 nm (APC). The IC50 value is then obtained.
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| Cell Assay |
Cells are plate at a density of 1×104 cells per well in clear flat-bottomed 96-well plates and incubated overnight. Following media aspiration from the plates and a single PBS wash in cold water, the incubation process is complete. Each well receives 80 μL of MSD Lysis buffer, and the plates are shaken at 4°C for at least 30 minutes before use. Plates are washed four times with 200 L/well wash buffer for the Akt duplex assay and then blotted with paper towels. After that, each well receives 60 μL of lysates, and the plates are shaken at room temperature for 1 hour.
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| Animal Protocol |
Xenograft mice models of BT474 or HCC1954 cells
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| References | |
| Additional Infomation |
GSK1059615 is a thiazolidinone that is the 5-{[4-(pyridin-4-yl)quinolin-6-yl]methylene} derivative of 1,3-thiazolidine-2,4-dione. A PI3K inhibitor It has a role as an EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor and an antineoplastic agent. It is a member of quinolines, a member of pyridines and a thiazolidinone.
GSK1059615 has been used in trials studying the treatment of Lymphoma, Solid Tumours, Endometrial Cancer, Solid Tumor Cancer, and Metastatic Breast Cancer. PI3K Inhibitor GSK1059615 is a phosphoinositide 3-kinase (PI3K) inhibitor with potential antineoplastic activity. PI3K inhibitor GSK1059615 inhibits PI3K in the PI3K/AKT kinase signaling pathway, which may trigger the translocation of cytosolic Bax to the mitochondrial outer membrane and an increase in mitochondrial membrane permeability, followed by apoptosis. Bax is a member of the proapoptotic Bcl-2 family of proteins. PI3K, an enzyme often overexpressed in cancer cells, plays a crucial role in tumor cell regulation and survival. |
| Molecular Formula |
C18H11N3O2S
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|---|---|
| Molecular Weight |
333.36384
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| Exact Mass |
333.057
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| Elemental Analysis |
C, 64.85; H, 3.33; N, 12.60; O, 9.60; S, 9.62
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| CAS # |
958852-01-2
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| Related CAS # |
958852-01-2; 1356195-42-0 (sodium salt hydrate);
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| PubChem CID |
23582824
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| Appearance |
Light yellow to brown solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.759
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| LogP |
1.78
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
24
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| Complexity |
544
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(=C1/C(=O)NC(=O)S/1)\C1C=CC2C(=C(C3C=CN=CC=3)C=CN=2)C=1
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| InChi Key |
SSROGLWTGKZPRA-MHWRWJLKSA-N
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| InChi Code |
InChI=1S/C18H11N3O2S/c22-17-16(21-18(23)24-17)10-11-1-2-15-14(9-11)13(5-8-20-15)12-3-6-19-7-4-12/h1-10H,(H,21,23)/b16-10+
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| Chemical Name |
(E)-4-((4-(pyridin-4-yl)quinolin-6-yl)methylene)thiazolidine-2,5-dione
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| Synonyms |
GSK-1059615; GSK-1059615; GSK1059615
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~2 mg/mL (6.0 mM)
Water: <1 mg/mL Ethanol: <1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 0.5 mg/mL (1.50 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 0.5 mg/mL (1.50 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 5.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 0.5 mg/mL (1.50 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9998 mL | 14.9988 mL | 29.9976 mL | |
| 5 mM | 0.6000 mL | 2.9998 mL | 5.9995 mL | |
| 10 mM | 0.3000 mL | 1.4999 mL | 2.9998 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00695448 | Terminated | Drug: GSK1059615 | Solid Tumours | GlaxoSmithKline | June 24, 2008 | Phase 1 |
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