受注:045-509-1970 |
技術サポート:[email protected] 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
Synonyms | GTPL7939 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
|
化学式 | C20H23ClN6O2 |
|||
分子量 | 414.89 | CAS No. | 1224887-10-8 | |
Solubility (25°C)* | 体外 | DMSO | 82 mg/mL (197.64 mM) | |
Ethanol | 82 mg/mL (197.64 mM) | |||
Water | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | GSK2256098 is a potent, selective, reversible, and ATP competitive FAK kinase inhibitor with apparent Ki of 0.4 nM. GSK2256098 inhibits cancer cell growth and induces apoptosis. |
---|---|
in vitro | GSK2256098 has been developed to inhibit FAK activity through targeting the phosphorylation site of FAK, tyrosine (Y) 397. After a 30-min incubation, GSK2256098 inhibits FAK activity or Y397 phosphorylation in cancer cell lines, OVCAR8 (ovary), U87MG (brain), and A549 (lung), at IC50 values of 15, 8.5 and 12 nM, respectively. In addition, the data suggests that cellular inhibition of FAK by GSK2256098 can occur as early as 30 min in cultured cells and lasts up to 12 hours in mouse tumor xenografts. GSK2256098 inhibition of FAK kinase activity can decrease Akt and ERK activity. PI3K/Akt and ERK signaling contributes to cell survival, implying a pharmacological value of GSK2256098 in attenuation of abnormal survival pathways in specific types of PDAC cells. GSK2256098 can promote apoptosis in L3.6P1 cells through caspase-9/PARP-related pathways. It attenuates abnormal growth and aberrant motility of PDAC cells in a FAK specific manner[1]. GSK2256098 also inhibits growth, migration, and invasion and induces apoptosis in a subset of GBM cell lines[2]. |
in vivo | Pharmacokinetic (PK) studies in mice and rats with an intact blood brain barrier indicate that the penetration of GSK2256098 into the CNS is poor. However, it achieves concentrations in tumor of patients with GBM(glioblastoma) exceeding those associated with preclinical activity[2]. GSK2256098 has an acceptable safety profile, has evidence of target engagement at doses at or below the MTD (maximum tolerated dose), and has clinical activity in patients with mesothelioma, particularly those with merlin loss[3]. In the Ishikawa orthoptopic murine model, treatment with GSK2256098 results in lower tumor weights and fewer metastases than mice inoculated with Hec1A cells. Tumors treated with GSK2256098 have lower microvessel density (CD31), less cellular proliferation (Ki67), and higher apoptosis (TUNEL) rates in the Ishikawa model when compared to the Hec1a model. GSK2256098 may be therapeutically beneficial to patients with PTEN-mutant uterine cancer, and PTEN represents a potential predictive biomarker[4]. |
細胞アッセイ | 細胞株 | PDAC(pancreatic ductal adenocarcinoma) cells |
---|---|---|
濃度 | 0.1–10 μM | |
反応時間 | 48 or 72 h | |
実験の流れ | PDAC cells are cultured on a 6-well plate. When cell confluence reachs 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. |
|
動物実験 | 動物モデル | athymic nude mice |
投薬量 | 75 mg/kg | |
投与方法 | oral administration |
FAK suppresses antigen processing and presentation to promote immune evasion in pancreatic cancer [ Gut, 2023, gutjnl-2022-327927] | PubMed: 36977556 |
FAK suppresses antigen processing and presentation to promote immune evasion in pancreatic cancer [ Gut, 2023, 1–2] | PubMed: None |
YAP Inactivation by Soft Mechanotransduction Relieves MAFG for Tumor Cell Dedifferentiation [ Research (Wash D C), 2023, 6:0215] | PubMed: 37614365 |
YAP Inactivation by Soft Mechanotransduction Relieves MAFG for Tumor Cell Dedifferentiation [ Research -Wash D C), 2023, 6:0215] | PubMed: 37614365 |
CCN1 interacts with integrins to regulate intestinal stem cell proliferation and differentiation [ Nat Commun, 2022, 13(1):3117] | PubMed: 35660741 |
Loss of non-motor kinesin KIF26A causes congenital brain malformations via dysregulated neuronal migration and axonal growth as well as apoptosis [ Dev Cell, 2022, 57(20):2381-2396.e13] | PubMed: 36228617 |
ERK phosphorylation is dependent on cell adhesion in a subset of pediatric sarcoma cell lines [ Biochim Biophys Acta Mol Cell Res, 2022, 1869(8):119264] | PubMed: 35381293 |
Self-renewal or quiescence? Orchestrating the fate of mesenchymal stem cells by matrix viscoelasticity via PI3K/Akt-CDK1 pathway [ Biomaterials, 2021, 279:121235] | PubMed: 34749070 |
AhR and Cancer: From Gene Profiling to Targeted Therapy [ Int J Mol Sci, 2021, 22(2)E752] | PubMed: 33451095 |
Crispr/Cas-based modeling of NF2 loss in meningioma cells [ J Neurosci Methods, 2021, 356:109141] | PubMed: 33753124 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。