VS-4718 (PND-1186)

製品コードS7653 バッチS765303

化学情報

	Synonyms	SR-2156	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₅H₂₆F₃N₅O₃
	分子量	501.5	CAS No.	1061353-68-1
Solubility (25°C)*	体外	DMSO	100 mg/mL (199.4 mM)
		Ethanol	3 mg/mL (5.98 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	VS-4718 (PND-1186) is a reversible and selective FAK inhibitor with IC50 of 1.5 nM. PND-1186 selectively promotes tumor cell apoptosis. Phase 1.
in vitro	In vitro, PND-1186 inhibits 4T1 breast carcinoma motility, promotes 4T1 apoptosis in suspended conditions, and decreases 4T1 soft agar colony number and size. ^[1] In HEY and OVCAR8 cells, VS-4718 promotes G0-G1 cell-cycle arrest followed by cell death. ^[2]
in vivo	In mice bearing 4T1 tumors, PND-1186 (100 mg/kg s.c.) inhibits 4T1 subcutaneous tumor growth by induction of apoptosis. In mice bearing ID8 tumors, PND-1186 (0.5 mg/mL for p.o.) also causes ovarian carcinoma tumor growth inhibition. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	In vitro kinase activity
キナーゼアッセイ	GST-FAK in vitro kinase activity is measured and compared to His-tagged FAK 411–686 using the K-LISA screening kit and poly(Glu:Tyr) (4:1) copolymer as a substrate immobilized on microtiter plates. IC50 values are determined with various concentrations of test compounds in a buffer containing 50 µM ATP and 10 mM MnCl₂, 50 mM HEPES (pH 7.5), 25 mM NaCl, 0.01% BSA, and 0.1 mM Na orthovanadate for 5 min at room temperature. Serial diluted compounds are tested in triplicate. Substrate phosphorylation is measured using horseradish peroxidase-conjugated anti-pTyr antibodies with spetrophotometric color quantitation. IC50 values are determined using the Hill-Slope Model. Kinase selectivity profiling is performed by using the KinaseProfiler service.
細胞アッセイ	細胞株	Murine ID8 ovarian carcinoma cells
	濃度	~1 μM
	反応時間	6 days
	実験の流れ	For soft agar assays, 48-well plates are coated with a 1:4 mix of 2% agar (EM Science) in 0.2 mL growth media (bottom layer). 5×10⁴ cells are plated per well (in triplicate) in a mixture of 0.3% agar in 0.2 mL growth media (top layer). After agar solidification, 0.2 mL growth media is added containing DMSO or PND-1186 (final concentration for 0.6 mL). In separate experiments, PND-1186 is added after 4 days. After 10 days, colonies are imaged in phase contrast, enumerated by counting 9 fields (3 fields per well), and total area determined using Image J. For all analyses, experimental points are performed in triplicate and repeated at least two times.
動物実験	動物モデル	Mice bearing ID8 tumors or 4T1 tumors
	投薬量	100 mg/kg every 12 hours for s.c.; 0.5 mg/mL for p.o.
	投与方法	s.c. or p.o.

参考

カスタマーフィードバック

: , , Cell Death Differ, 2017, 24(5):889-902

: , , Oncogene, 2017, 36(39):5522-5531

: Data from [Data independently produced by , , Molecular and Cellular Biology, 2016, 36(10):1555-1568.]

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：

Pivotal role of IL-8 derived from the interaction between osteosarcoma and tumor-associated macrophages in osteosarcoma growth and metastasis via the FAK pathway [ Cell Death Dis, 2024, 15(2):108]	PubMed: 38302407
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
Stiff matrix induces exosome secretion to promote tumour growth [ Nat Cell Biol, 2023, 25(3):415-424]	PubMed: 36797475
VE-Cadherin modulates β-catenin/TCF-4 to enhance Vasculogenic Mimicry [ Cell Death Dis, 2023, 14(2):135]	PubMed: 36797281
Overcoming resistance of stroma-rich pancreatic cancer with focal adhesion kinase inhibitor combined with G47Δ and immune checkpoint inhibitors [ Mol Ther Oncolytics, 2023, 28:31-43]	PubMed: 36619294
FAK mediates LPS-induced inflammatory lung injury through interacting TAK1 and activating TAK1-NFκB pathway [ Cell Death Dis, 2022, 13(7):589]	PubMed: 35803916
TM4SF1 promotes esophageal squamous cell carcinoma metastasis by interacting with integrin α6 [ Cell Death Dis, 2022, 13(7):609]	PubMed: 35835740
Low-dose X-ray irradiation combined with FAK inhibitors improves the immune microenvironment and confers sensitivity to radiotherapy in pancreatic cancer [ Biomed Pharmacother, 2022, 151:113114]	PubMed: 35594704
Ovarian Cancer Cells in Ascites Form Aggregates That Display a Hybrid Epithelial-Mesenchymal Phenotype and Allows Survival and Proliferation of Metastasizing Cells [ Int J Mol Sci, 2022, 23(2)833]	PubMed: 35055018

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。