NPS-1034

製品コードS7669 バッチS766901

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₃₁H₂₃F₂N₅O₃

分子量

551.54

CAS No.

1221713-92-3

Solubility (25°C)*

体外

DMSO (warmed with 50ºC water bath)

100 mg/mL (181.31 mM)

Ethanol

4 mg/mL (7.25 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Clear solution

PBS

11.0mg/ml

* <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	NPS-1034 is a dual Met (c-Met)/Axl inhibitor with IC50 of 48 nM and 10.3 nM, respectively.
in vitro	In HCC827/GR cells, NPS-1034 does not show significant antiproliferative effects, while overcomes gefitinib resistance by inhibiting the phosphorylation of MET, Akt, and Erk. In H820 cells, NPS-1034 enhances sensitivity to EGFR-TKIs. In HCC78 cells, NPS-1034 inhibits ROS1 activity and cell proliferation. In addition, a combination of gefitinib and NPS-1034 enhances cell death by inducing caspase-3 and PARP-1 cleavage. ^[1] NPS-1034 inhibits the viability of the MKN45 and SNU638 cell lines, which highly express the MET gene and p-MET, with IC50 of 112.7 and 190.3 nmol, respectively. ^[2]
in vivo	In SCID mice bearing HCC827/GR tumor xenografts, NPS-1034 (10 mg/kg, p.o.) decreases tumor growth, and the combination of gefitinib and NPS-1034 results in enhanced tumor growth inhibition via the inhibition of tumor proliferation and the induction of apoptosis. ^[1] In nude mice bearing MKN45 xenograft tumors, NPS-1034 (30 mg/kg, p.o.) decreases tumor growth through the inhibition of angiogenesis and the promotion of apoptosis. ^[2]

プロトコル(参考用のみ)

キナーゼアッセイ	Kinase inhibition profile
キナーゼアッセイ	The in vitro NPS-1034 profile of inhibition of RTKs is analyzed using RTK assay kits according to the manufacturer's protocols.
細胞アッセイ	細胞株	HCC827/GR, HCC-78 and H820 cells
	濃度	~5 μM
	反応時間	72 h
	実験の流れ	To perform the MTT assay, cells (0.5 × 10⁴/well) are plated in 96-well sterile plastic plates and allowed to attach overnight. Cells are exposed to varying doses of gefitinib, erlotinib, PHA-665752, and NPS-1034 in medium containing 1% FBS. After 72 hours, 15 μL of MTT solution (5 mg/mL) is added to each well and plates are incubated for 4 hours. Crystalline formazan is solubilized with 100 μL of a 10% (w/v) SDS solution for 24 hours. Absorbance at 595 nm is read spectrophotometrically using a microplate reader.
動物実験	動物モデル	SCID mice bearing HCC827/GR tumor xenografts
	投薬量	10 mg/kg, 5 days a week
	投与方法	p.o.

参考

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：

Inhibition of AXL receptor tyrosine kinase enhances brown adipose tissue functionality in mice [ Nat Commun, 2023, 14(1):4162]	PubMed: 37443109
Generating Selective Leads for Mer Kinase Inhibitors-Example of a Comprehensive Lead-Generation Strategy [ J Med Chem, 2021, 64(6):3165-3184]	PubMed: 33683117
Contribution of p53 in sensitivity to EGFR tyrosine kinase inhibitors in non-small cell lung cancer [ Sci Rep, 2021, 11(1):19667]	PubMed: 34608255

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。