| Size | Price | Stock | Qty |
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| 2mg |
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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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Purity: =99.23%
GSK2256098 is a small molecule developed by GlaxoSmithKline) as a selective FAK (Focal Adhesion Kinase) kinase inhibitor to inhibit FAK activity through targeting the phosphorylation site of FAK, tyrosine (Y) 397. The growth and survival of pancreatic ductal adenocarcinoma cells are inhibited by GSK2256098. When compared to Pyk2, the closest member of the FAK family, it is a thousand times more selective for FAK. By specifically targeting the phosphorylation site of FAK, tyrosine (Y) 397, GSK2256098 inhibits FAK activity. PTEN-mutant (Ishikawa) cells treated with GSK2256098 showed a higher degree of pFAK(Y397) inhibition than PTEN-wild-type (Hec1A) cells. Hec1A cells that had not been treated were less sensitive to GSK2256098 than Ishikawa cells. Ishikawa cells were transfected with a wild-type PTEN construct, and following GSK2256098 treatment, the expression of pFAK(Y397) remained unaltered. When paclitaxel and topotecan were combined with GSK2256098, Ishikawa cells showed decreased cell viability and increased sensitivity to the treatment, in contrast to Hec1a cells.
| Targets |
FAK (Ki = 0.4 nM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
The closest member of the FAK family, Pyk2, is a thousand times less selective for FAK than GSK2256098. By focusing on FAK's phosphorylation site, tyrosine (Y) 397, GSK2256098 suppresses FAK activity. For OVCAR8 (ovary), U87MG (brain), and A549 (lung) cancer cell lines, GSK2256098 inhibits FAK activity or Y397 phosphorylation at IC50s of 15, 8.5, and 12 nM, respectively.
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| Cell Assay |
On the wells of a 96-well plate, PDAC cells are grown. The wells are filled with 10 microliters of MTS (100 μL total). The absorbance at 450 nm wave length of reacted MTS is measured on a microplate reader after the plate is incubated for 10 to 30 minutes at 37°C. GSK2256098's IC50 on cell viability is determined using the Sigma plot program. Using a 6-well plate, PDAC cells are grown. The cells are incubated in the medium containing 0.1–10 μM GSK2256098 for 48 or 72 hours after cell confluence in regular medium reaches roughly 70%. Cells are reseeded at the conclusion of treatments and stored for nine days. The blue colonies are then counted after the cells are stained with clonogenic reagent[1].
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| Animal Protocol |
Mice: The mice used are female athymic nude mice aged 8–12 weeks. In experimental therapy, 4x106 Ishikawa or Hec1A cells are injected into the uterus horn. The mice are randomized (n = 10 mice per group) based on the following groups after receiving tumor cell injection: 1) 100 microliters of a vehicle control (orally, daily); 2) 75 milligrams per kilogram of GSK2256098 in 100 microliters of vehicle (orally, daily); 3) 2.5 milligrams per kilogram of Paclitaxel in 200 microliters of PBS (intraperitoneally, weekly); and 4) GSK2256098 and Paclitaxel (doses and frequencies mentioned above). After the tumor injection, therapy is started 10–14 days later. Four to six weeks after treatment initiation, the mice are checked for side effects and cervically dislocated for death. Each mouse's weight, the total weight of the tumor, the location and quantity of tumor nodules are noted for each treatment group at the end of the experiment. In order to process tumor samples for additional analysis, they are either frozen in a medium with the ideal cutting temperature or paraffin-embedded in a section fixed in formalin.
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| References |
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| Molecular Formula |
C20H23CLN6O2
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| Molecular Weight |
414.89
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| Exact Mass |
414.16
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| Elemental Analysis |
C, 57.90; H, 5.59; Cl, 8.54; N, 20.26; O, 7.71
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| CAS # |
1224887-10-8
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| Related CAS # |
1416771-10-2 (HCl);1224887-10-8;
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| Appearance |
White to off-white solid powder
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| SMILES |
CC1=NN(C(=C1)NC2=NC=C(C(=C2)NC3=CC=CC=C3C(=O)NOC)Cl)C(C)C
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| InChi Key |
BVAHPPKGOOJSPU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H23ClN6O2/c1-12(2)27-19(9-13(3)25-27)24-18-10-17(15(21)11-22-18)23-16-8-6-5-7-14(16)20(28)26-29-4/h5-12H,1-4H3,(H,26,28)(H2,22,23,24)
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| Chemical Name |
2-[[5-chloro-2-[(5-methyl-2-propan-2-ylpyrazol-3-yl)amino]pyridin-4-yl]amino]-N-methoxybenzamide
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.03 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: ≥ 2.5 mg/mL (6.03 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4103 mL | 12.0514 mL | 24.1028 mL | |
| 5 mM | 0.4821 mL | 2.4103 mL | 4.8206 mL | |
| 10 mM | 0.2410 mL | 1.2051 mL | 2.4103 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 |
| NCT02523014 | Recruiting | Drug: Vismodegib Drug: FAK Inhibitor GSK2256098 |
Intracranial Meningioma NF2 Gene Mutation |
Alliance for Clinical Trials in Oncology |
August 2015 | Phase 2 |
| NCT02551653 | Completed | Drug: [11C]-GSK2256098 500 MBq | Hypertension, Pulmonary | GlaxoSmithKline | November 17, 2015 | Phase 1 |
| NCT02428270 | Completed | Drug: GSK2256098 Drug: Trametinib |
Pancreatic Cancer Adenocarcinoma |
University Health Network, Toronto | April 2016 | Phase 2 |
| NCT01938443 | Completed | Drug: GSK2256098 Drug: Trametinib |
Cancer Neoplasms |
GlaxoSmithKline | November 18, 2013 | Phase 1 |
| NCT01138033 | Completed | Drug: GSK2256098 | Cancer | GlaxoSmithKline | July 27, 2010 | Phase 1 |
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