GSK2256098

製品コードS8523 バッチS852302

化学情報

	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.

溶剤液（一定の濃度）を調合する

生物活性

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].

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].

プロトコル(参考用のみ)

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

参考

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Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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。

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