| 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: =98.87%
Omipalisib (also called GSK-2126458, GSK-458), a pyridylsulfonamide analog, is a potent, highly selective and orally bioavailable small-molecule inhibitor of phosphatidylinositol 3-kinase (PI3K) p110α/β/δ/γ with potential anticancer activity. It is a dual PI3K/mToR inhibitor that also inhibits mTORC1/2 with Ki values of 0.019 nM/0.13 nM/0.024 nM/0.06 nM and 0.18 nM/0.3 nM in cell-free assays, respectively. Omipalisib is a new investigational PI3K/mToR Inhibitor developed by GSK-Glaxo SmithKline and is currently undergoing clinical trials for cancer treatment.
| Targets |
p110α (Ki = 0.019 nM); p110α-E545K (Ki = 0.008 nM); p110α-E542K (Ki = 0.008 nM); p110α-H1047R (Ki = 0.009 nM); p110β (Ki = 0.13 nM); p110δ (Ki = 0.024 nM); p110γ (Ki = 0.06 nM); mTORC1 (Ki = 0.18 nM); mTORC2 (Ki = 0.3 nM)
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| ln Vitro |
GSK2126458 potently inhibits the activity of common activating mutants of p110α (E542K, E545K, and H1047R) found in human cancer with Ki of 8 pM, 8 pM and 9 pM, respectively.[1] GSK2126458 significantly lowers the levels of pAkt-S473 in T47D and BT474 cells with a remarkable potency, with IC50 values of 0.41 nM and 0.18 nM, respectively. Additionally, GSK2126458 causes a G1 cell cycle arrest and has an inhibitory effect on cell proliferation in a variety of cell lines, including the T47D and BT474 breast cancer lines with IC50 values of 3 nM and 2.4 nM, respectively.[1]
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| ln Vivo |
In a BT474 human tumor xenograft model, GSK2126458 treatment reduces pAkt-S473 levels in a dose-dependent manner and inhibits tumor growth in a dose-dependent manner at a low dose of 300 μg/kg. The oral bioavailability of GSK2126458 is also good in four preclinical species (mouse, rat, dog, and monkey), and its blood clearance is low.[1]
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| Enzyme Assay |
The Multidrop Combi is used to add 2.5 μL of stop solution (Stop A and Stop B pre-mixed at a ratio of 5:1, respectively) to all wells in order to quench reactions. The quenched reactions are then processed to identify product formation by adding 2.5 μL of detection solution using the Multidrop Combi (Detection mix C, Detection mix A, and Detection mix B combined together in an 18:1:1 ratio, i.e., for a 6000 μL total volume, mix 5400 μL Detection mix C, 300 μL Detection mix A, and 300 μL Detection mix B).
Please take note that this solution needs to be prepared two hours before use. The HTRF signal is measured on the Envision plate reader set for 330nm excitation after an hour of dark incubation.
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| Cell Assay |
BT474, HCC1954 and T-47D (human breast) are cultured in RPMI-1640 containing 10% fetal bovine serum at 37 °C in 5% CO2 incubator. Prior to assay setup, cells are divided into T75 flasks at a density that results in 70–80% confluence at the time of assay harvest. Trypsin-EDTA 0.25% is used to harvest cells. Utilizing Trypan Blue exclusion staining, cell counts are carried out on cell suspension. Then, cells are plated in 384-well black flat-bottom polystyrene dishes with 1,000 cells per well and 48 μL of culture medium per dish. GSK2126458 is added the following day after all plates have been overnighted at 5% CO2, 37 °C. One plate is given a CellTiter-Glo treatment for a day 0 (t=0) measurement and read as per the instructions below. GSK2126458 is made in 384 well clear bottom polypropylene plates using successive two fold dilutions. 2 μL of these dilutions are added to each well of the cell plates after 4 μL of these dilutions are added to 105 μL of culture media and the solution is mixed. The final DMSO concentration in each well is 0.15%. 72 hours are spent incubating the cells at 37 °C and 5% CO2. Each plate is developed and read 72 hours after being incubated with GSK2126458. Using a volume equal to the cell culture volume in the wells, CellTiter-Glo reagent is added to assay plates. After about 30 minutes of incubation at room temperature and two minutes of shaking, the plates are read using the Analyst GT reader for the chemiluminescent signal. Results are plotted against the concentration of GSK2126458 and expressed as a percentage of the t=0. For GSK2126458, the concentration (gIC50) that inhibits 50% of the cell growth with Y min as the t=0 and Y max as the DMSO control is determined by fitting the dose response with a 4 or 6 parameter curve fit using the XLfit software. For background correction, the value from wells without cells is subtracted from all samples.
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| Animal Protocol |
Human BT474 tumors implanted in mice.
≤300 μg /kg Administered via p.o. |
| References |
| Molecular Formula |
C25H17F2N5O3S
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|---|---|
| Molecular Weight |
505.4960
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| Exact Mass |
505.10202
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| Elemental Analysis |
C, 59.40; H, 3.39; F, 7.52; N, 13.85; O, 9.50; S, 6.34
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| CAS # |
1086062-66-9
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| Related CAS # |
1086062-66-9
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| Appearance |
light yellow solid powder
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| SMILES |
COC1=C(C=C(C=N1)C2=CC3=C(C=CN=C3C=C2)C4=CN=NC=C4)NS(=O)(=O)C5=C(C=C(C=C5)F)F
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| InChi Key |
CGBJSGAELGCMKE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H17F2N5O3S/c1-35-25-23(32-36(33,34)24-5-3-18(26)12-21(24)27)11-17(13-29-25)15-2-4-22-20(10-15)19(7-8-28-22)16-6-9-30-31-14-16/h2-14,32H,1H3
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| Chemical Name |
2,4-difluoro-N-[2-methoxy-5-(4-pyridazin-4-ylquinolin-6-yl)pyridin-3-yl]benzenesulfonamide
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| Synonyms |
Omipalisib; GSK2126458; GSK 2126458; GSK-2126458
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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: ~100 mg/mL (~197.8 mM)
Water: <1 mg/mL Ethanol: <1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: 1%DMSO+30% polyethylene glycol+1%Tween 80: 18mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9782 mL | 9.8912 mL | 19.7824 mL | |
| 5 mM | 0.3956 mL | 1.9782 mL | 3.9565 mL | |
| 10 mM | 0.1978 mL | 0.9891 mL | 1.9782 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 | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00972686 | Completed | Drug: GSK2126458 | Solid Tumor | GlaxoSmithKline | August 31, 2009 | Phase 1 |
| NCT01725139 | Completed | Drug: Placebo Drug: GSK2126458 |
Idiopathic Pulmonary Fibrosis | GlaxoSmithKline | March 8, 2013 | Phase 1 |
Greger JG, et al. Mol Cancer Ther. 2012, 11(4), 909-920. |
Developing selective type II kinase inhibitors. (A) Docking imatinib into the X-ray co-crystal structure of DDR1. (B) Chemical structure of DDR1-IN-1/2 and representative developing rationale.ACS Chem Biol.2013 Oct 18;8(10):2145-50. |
Combinatorial Screening of DDR1-IN-1/2 with the LINCS library against the SNU-1040 cell line.ACS Chem Biol.2013 Oct 18;8(10):2145-50. |
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