1. Protein Tyrosine Kinase/RTK
  2. FAK

GSK2256098 

Cat. No.: HY-100498 Purity: 99.35%
Data Sheet SDS Handling Instructions

GSK2256098 is a selective FAK kinase inhibitor, which inhibits growth and survival of pancreatic ductal adenocarcinoma cells.

For research use only. We do not sell to patients.
GSK2256098 Chemical Structure

GSK2256098 Chemical Structure

CAS No. : 1224887-10-8

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $91 In-stock
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5 mg $100 In-stock
10 mg $150 In-stock
25 mg $300 In-stock
50 mg $540 In-stock
100 mg $970 In-stock
200 mg $1750 In-stock
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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

GSK2256098 is a selective FAK kinase inhibitor, which inhibits growth and survival of pancreatic ductal adenocarcinoma cells.

IC50 & Target

FAK[1]

In Vitro

GSK2256098 is a thousand fold more selective for FAK compared to the nearest FAK family member, Pyk2. GSK2256098 inhibits FAK activity through targeting the phosphorylation site of FAK, tyrosine (Y) 397. GSK2256098 inhibits FAK activity or Y397 phosphorylation in cancer cell lines, OVCAR8 (ovary), U87MG (brain), and A549 (lung), at IC50s of 15, 8.5 and 12 nM, respectively. The responses of 6 PDAC cell lines in regards to FAK Y397 phosphorylation or activity to GSK2256098 treatments (0.1–10 μM) ranged from low (less than 20% inhibition) to high (more than 90% inhibition). The least and most sensitive cell lines (PANC-1 and L3.6P1) are selected for further analysis. GSK2256098 inhibition of FAK Y397 phosphorylation correlated with decreased levels of phosphorylated Akt and ERK in L3.6P1 cells. GSK2256098 decreases cell viability, anchorage-independent growth, and motility in a dose dependent manner[1].

In Vivo

FAK is well-known to play an important role in angiogenesis, proliferation, and apoptosis, so the tumor samples harvested from the therapy experiments are examined. Evaluating CD31, significantly lower microvessel densities in tumors from mice treated with GSK2256098 and Paclitaxel is observed than in tumors from mice in the vehicle control group (P<0.05). This is consistent across both models, but Ishikawa tumors had the lowest microvessel density. All tumor models in mice treated with GSK2256098 exhibit less proliferation via Ki67 than control. Ishikawa tumors have the lowest Ki67 expression in response to therapy. Ishikawa tumors have higher apoptotic indices than Hec1A tumors after treatment with GSK2256098. Significant rates of apoptosis are seen in all models that had been treated with combination GSK2256098 and Paclitaxel[2].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT02428270 University Health Network, Toronto|GlaxoSmithKline Pancreatic Cancer|Adenocarcinoma April 2016 Phase 2
NCT02551653 GlaxoSmithKline Hypertension, Pulmonary November 2015 Phase 1
NCT01938443 GlaxoSmithKline Cancer November 18, 2013 Phase 1
NCT01138033 GlaxoSmithKline Cancer July 27, 2010 Phase 1
NCT00996671 GlaxoSmithKline Cancer November 6, 2009 Phase 1
NCT02523014 Alliance for Clinical Trials in Oncology|National Cancer Institute (NCI)|GlaxoSmithKline|Genentech, Inc.|Brain Science Foundation Intracranial Meningioma|Recurrent Meningioma|NF2 Gene Mutation August 2015 Phase 2
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References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 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
Cell Assay
[1]

GSK2256098 is dissolved in DMSO and stored, and then diluted with appropriate medium before use[1].

PDAC cells are cultured on the wells of a 96-well plate. Ten microliters of MTS is added to the wells (total value: 100 μL). After the plate is kept in a 37°C incubator for 10-30 min, the absorbance at 450 nm wave length of reacted MTS is determined on a microplate reader. The Sigma plot program is used to calculate IC50 of GSK2256098 on cell viability. PDAC cells are cultured on a 6-well plate. When cell confluence reached about 70% in regular medium, the cells are incubated in the medium containing 0.1-10 μM GSK2256098 for 48 or 72 hr. At the end of treatments, cells are re-seeded and kept for 9 d Then, the cells are stained using Clonogenic Reagent, and the blue colonies are counted[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

GSK2256098 is dissolved in DMSO and then diluted with PBS or saline[2].

Mice[2]
Female 8- to 12-week-old athymic nude mice are used. For therapeutic experiments, 4×106 Ishikawa or Hec1A cells are inoculated into the uterine horn. Following tumor cell injection, the mice are randomized (n=10 mice per group) according to the following groups: 1) 100 μL of a vehicle control (oral, daily); 2) 75 mg/kg GSK2256098 in 100 μL of vehicle (oral, daily); 3) 2.5 mg/kg Paclitaxel in 200 μL of PBS (intraperitoneal, weekly); and 4) GSK2256098 and Paclitaxel (doses and frequencies given above). Therapy is initiated 10-14 days after tumor injection. The mice are monitored for adverse effects and sacrificed using cervical dislocation four to six weeks after initiation of treatment. At the completion of each experiment, each mouse’s weight, aggregate tumor weight, location, and number of tumor nodules are recorded for each treatment group. Tumor samples are processed for further analysis via preservation in optimal cutting temperature medium for frozen section analysis as well as fixed in formalin for paraffin-embedded section analysis. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

414.89

Formula

C₂₀H₂₃ClN₆O₂

CAS No.

1224887-10-8

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 30 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 99.35%

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GSK2256098
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