PHA-665752

製品コード：S1070 純度：99.91%

PHA-665752 is a potent, selective and ATP-competitive c-Met inhibitor with IC50 of 9 nM in cell-free assays, >50-fold selectivity for c-Met than RTKs or STKs.

CAS No. 477575-56-7

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
5mg	JPY 22000	国内在庫あり
10mg	JPY 37000	国内在庫あり
50mg	JPY 88500	国内在庫あり
1g	JPY 538500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（94）

製品安全説明書

現在のバッチを見る：純度： 99.91%

99.91

PHA-665752関連製品

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関連化合物ライブラリー	Kinase Inhibitor Library Tyrosine Kinase Inhibitor Library PI3K/Akt Inhibitor Library Cell Cycle compound library Angiogenesis Related compound Library	もっと見る

シグナル伝達経路

c-Metシグナル伝達経路

c-Met阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	活性情報	PMID
LC-2-ad	Growth Inhibition Assay	IC50=49.1413 μM	SANGER
NCI-H2171	Growth Inhibition Assay	IC50=46.0272 μM	SANGER
HH	Growth Inhibition Assay	IC50=43.5069 μM	SANGER
CCRF-CEM	Growth Inhibition Assay	IC50=42.2797 μM	SANGER
EW-18	Growth Inhibition Assay	IC50=40.8303 μM	SANGER
NCI-H510A	Growth Inhibition Assay	IC50=38.2032 μM	SANGER
BC-1	Growth Inhibition Assay	IC50=38.033 μM	SANGER
IMR-5	Growth Inhibition Assay	IC50=37.4318 μM	SANGER
KU812	Growth Inhibition Assay	IC50=34.5702 μM	SANGER
KS-1	Growth Inhibition Assay	IC50=33.9481 μM	SANGER
SW962	Growth Inhibition Assay	IC50=33.4513 μM	SANGER
MONO-MAC-6	Growth Inhibition Assay	IC50=32.8795 μM	SANGER
NB7	Growth Inhibition Assay	IC50=32.2665 μM	SANGER
EW-13	Growth Inhibition Assay	IC50=29.5045 μM	SANGER
VA-ES-BJ	Growth Inhibition Assay	IC50=29.3729 μM	SANGER
697	Growth Inhibition Assay	IC50=28.7633 μM	SANGER
MOLT-13	Growth Inhibition Assay	IC50=27.1847 μM	SANGER
COLO-800	Growth Inhibition Assay	IC50=27.17 μM	SANGER
TE-11	Growth Inhibition Assay	IC50=26.069 μM	SANGER
ACN	Growth Inhibition Assay	IC50=22.2497 μM	SANGER
SK-N-DZ	Growth Inhibition Assay	IC50=21.2131 μM	SANGER
RPMI-8402	Growth Inhibition Assay	IC50=20.3269 μM	SANGER
LXF-289	Growth Inhibition Assay	IC50=19.8629 μM	SANGER
KE-37	Growth Inhibition Assay	IC50=19.8233 μM	SANGER
NB14	Growth Inhibition Assay	IC50=19.5425 μM	SANGER
NCI-H720	Growth Inhibition Assay	IC50=18.771 μM	SANGER
EoL-1-cell	Growth Inhibition Assay	IC50=18.4545 μM	SANGER
SCC-15	Growth Inhibition Assay	IC50=18.3498 μM	SANGER
TE-15	Growth Inhibition Assay	IC50=16.5771 μM	SANGER
KNS-81-FD	Growth Inhibition Assay	IC50=15.5849 μM	SANGER
NALM-6	Growth Inhibition Assay	IC50=15.2196 μM	SANGER
ES5	Growth Inhibition Assay	IC50=14.467 μM	SANGER
HT-144	Growth Inhibition Assay	IC50=14.2163 μM	SANGER
GI-1	Growth Inhibition Assay	IC50=11.8596 μM	SANGER
DOHH-2	Growth Inhibition Assay	IC50=10.9264 μM	SANGER
NCI-H1395	Growth Inhibition Assay	IC50=10.8024 μM	SANGER
ETK-1	Growth Inhibition Assay	IC50=10.2931 μM	SANGER
CTV-1	Growth Inhibition Assay	IC50=9.85024 μM	SANGER
EW-16	Growth Inhibition Assay	IC50=9.6543 μM	SANGER
A498	Growth Inhibition Assay	IC50=8.28446 μM	SANGER
ES6	Growth Inhibition Assay	IC50=7.8195 μM	SANGER
EW-22	Growth Inhibition Assay	IC50=7.73614 μM	SANGER
NCI-SNU-1	Growth Inhibition Assay	IC50=5.63733 μM	SANGER
Becker	Growth Inhibition Assay	IC50=5.2466 μM	SANGER
KM12	Growth Inhibition Assay	IC50=4.418 μM	SANGER
NOS-1	Growth Inhibition Assay	IC50=4.39867 μM	SANGER
ES1	Growth Inhibition Assay	IC50=3.34866 μM	SANGER
MRK-nu-1	Growth Inhibition Assay	IC50=2.40056 μM	SANGER
SUP-T1	Growth Inhibition Assay	IC50=2.13964 μM	SANGER
MV-4-11	Growth Inhibition Assay	IC50=1.2947 μM	SANGER
SK-LMS-1	Growth Inhibition Assay	IC50=0.89846 μM	SANGER
ALL-PO	Growth Inhibition Assay	IC50=0.81277 μM	SANGER
KINGS-1	Growth Inhibition Assay	IC50=0.35911 μM	SANGER
LB2241-RCC	Growth Inhibition Assay	IC50=0.15702 μM	SANGER
NCI-SNU-5	Growth Inhibition Assay	IC50=0.12375 μM	SANGER
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

PHA-665752 is a potent, selective and ATP-competitive c-Met inhibitor with IC50 of 9 nM in cell-free assays, >50-fold selectivity for c-Met than RTKs or STKs.

Targets

c-Met ^[1] (Cell-free assay)	RON ^[1] (Cell-free assay)	Flk1 ^[1] (Cell-free assay)
9 nM	68 nM	200 nM

In Vitro
In vitro	PHA-665752 significantly inhibits c-Met kinase activity with K_i of 4 nM, and exhibits >50-fold selectivity for c-Met compared with various tyrosine and serine-threonine kinases. PHA-665752 potently inhibits the HGF-stimulated c-Met autophosphorylation with IC50 of 25-50 nM. PHA-665752 also significantly blocks HGF- and c-Met-dependent functions such as cell motility and cell proliferation with IC50 of 40-50 nM and 18-42 nM, respectively. In addition, PHA-665752 potently inhibits HGF-stimulated or constitutive phosphorylation of mediators of downstream of c-Met such as Gab-1, ERK, Akt, STAT3, PLC-γ, and FAK in multiple tumor cell lines. ^[1] PHA-665752 inhibits cell growth in TPR-MET-transformed BaF3 cells with IC50 of <60 nM, and inhibits constitutive cell motility and migration by 92.5% at 0.2 μM. Inhibition of c-Met by PHA665752 (0.2 μM) also induces cell apoptosis of 33.1% and G1 cell cycle arrest with cells in G1 phase increasing from 42.4% to 77.0%. PHA665752 can cooperate with rapamycin to inhibit cell growth of TPR-MET-transformed BaF3 cells and non-small cell lung cancer H441 cells. ^[2]
Kinase Assay	In vitro enzyme assay
Kinase Assay	The c-Met kinase domain GST-fusion protein is used for the c-Met assay. The IC50 value of PHA-665752 for the inhibition of c-Met is based on phosphorylation of kinase peptide substrates or poly-glu-tyr in the presence of ATP and divalent cation (MgCl₂ or MnCl₂ 10-20 mM). The linear range (i.e., the time period over which the rate remains equivalent to the initial rate) is determined for c-Met, and the kinetic measurement and IC50 determination are performed within this range.
細胞実験	細胞株	S114, GTL-16, NCI-H441, and BxPC-3
	濃度	Dissolved in DMSO, final concentrations ~10 μM
	反応時間	18, or 72 hours
	実験の流れ	For proliferation assays, cells are grown in medium with 0.1% FBS for 48 hours after which they are treated with various concentrations of PHA-665752 in HGF (50 ng/mL) in a medium containing 2% FBS. After 18 hours, cells are incubated with BrdUrd for 1 hour, fixed, and stained with anti-BrdUrd peroxidase-conjugated antibody, and plates are read at 630 nm. For apoptosis assays, cells are grown in medium with 2% FBS in presence and absence of HGF (50 ng/mL) and various concentrations of PHA-665752 for 72 hours. After 72 hours, a mixture containing ethidium bromide and acridine orange is added, and apoptotic cells (bright orange cells or cell fragments) are counted by fluorescence microscopy.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	IDO p-Met / Met / p-Akt / Akt / p-ERK / ERK		27082119
	Growth inhibition assay	Cell proliferation		20603611

In Vivo
In Vivo	Administration of PHA-665752 induces a dose-dependent tumor growth inhibition of S114 xenografts by 20 %, 39% and 68%, at dose of 7.5, 15, and 30 mg/kg/day, respectively. ^[1] PHA665752 treatment significantly reduces the tumor growth of NCI-H69, NCI-H441 and A549 in mouse xenografts by 99%, 75%, and 59%, respectively. PHA665752 also significantly inhibits angiogenesis by >85%, due to decreasing the production of vascular endothelial growth factor and increasing the production of the angiogenesis inhibitor thrombospondin-1. ^[3]
動物実験	動物モデル	Female athymic mice (nu/nu) bearing S114 or GTL-16 tumor xenografts
	投与量	~30 mg/kg/day
	投与経路	Injection via bolus i.v.

参考
[1] Christensen JG, et al. Cancer Res, 2003, 63(21), 7345-7355. [2] Ma PC, et al. Clin Cancer Res, 2005, 11(6), 2312-2319. [3] Puri N, et al. Cancer Res, 2007, 67(8), 3529-3534.

参考

化学情報

分子量	641.61	化学式	C₃₂H₃₄Cl₂N₄O₄S
CAS No.	477575-56-7	SDF	Download PHA-665752 SDFをダウンロードする
Smiles	CC1=C(NC(=C1C(=O)N2CCCC2CN3CCCC3)C)C=C4C5=C(C=CC(=C5)S(=O)(=O)CC6=C(C=CC=C6Cl)Cl)NC4=O
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	１ケ月-20°Cin solvent

In vitro
Batch:

DMSO : 128 mg/mL ( (199.49 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 10 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

技術サポート

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Handling Instructions

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よくある質問（FAQ）

質問1:
I need to use S1070 for intraperitoneal application in mice. Could you tell me the solvent you use, please?

回答
The highest concentration of PHA-665752 (S1070) in 4% DMSO+30% PEG 300+5% Tween 80+ddH2O is 5mg/ml. If you want to get higher concentration, the concentration of DMSO and PEG will be higher. For example, it can be dissolved in 8% DMSO+50% PEG 300+5% Tween 80+ddH2O at 10mg/ml clearly.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):