Bosutinib

別名：SKI-606

製品コード：S1014 純度：99.94%

Bosutinib is a novel, dual Src/Abl inhibitor with IC50 of 1.2 nM and 1 nM in cell-free assays, respectively. Bosutinib also effectively decreases the activity of PI3K/AKT/mTOR, MAPK/ERK and JAK/STAT3 signaling pathways by blocking the phosphorylation levels of p-ERK, p-S6, and p-STAT3. Bosutinib promotes autophagy.

CAS No. 380843-75-4

サイズ	価格(税別)	在庫状況
10mg	JPY 22000	国内在庫あり
50mg	JPY 52000	国内在庫あり
200mg	JPY 104500	国内在庫あり
1g	JPY 220500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：sales@selleck.co.jp よく尋ねられる質問

文献中Selleckの製品使用例（141）

1/5

製品安全説明書

現在のバッチを見る：純度： 99.94%

99.94

Bosutinib関連製品

関連ターゲット	Lck Fyn Lyn Yes Fgr	もっと見る
関連製品	Saracatinib (AZD0530) PP2 SU6656 PP1 WH-4-023 Src Inhibitor 1 RK 24466 Myristic Acid eCF506 Tolimidone (MLR-1023) UM-164	もっと見る
関連化合物ライブラリー	Tyrosine Kinase Inhibitor Library PI3K/Akt Inhibitor Library Angiogenesis Related compound Library HIF-1 Signaling Pathway Compound Library FDA-approved Anticancer Drug Library	もっと見る

シグナル伝達経路

Srcシグナル伝達経路

Src阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Incubation Time	活性情報	PMID
K562	Cytotoxicity assay	72 hrs	Cytotoxicity against human K562 cells assessed as cell viability after 72 hrs by MTT assay, IC50 = 0.0043 μM.	26814890
HEK293	Function assay	1 hr	Inhibition of human full length PKMYT1 expressed in HEK293 cells using EFS (247 to 259 residues) as substrate after 1 hr by fluorescence polarization immunoasay, Ki = 0.0127 μM.	29941193
Ba/F3	Function assay	48 hrs	Inhibition of BCR-ABL1 E355G mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as inhibition of BCR-ABL1-mediated cell proliferation after 48 hrs by BriteLight luciferase assay, GI50 = 0.128 μM.	30137981
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

Targets

S6 kinase ^[7]	ERK ^[7]	STAT3 ^[7]	LCK ^[1]	Abl ^[2] (Cell-free assay)	もっとクリックする
				1 nM	もっとクリックする

In Vitro
In vitro	Bosutinib is selective for Src over non-Src family kinases with an IC50 of 1.2 nM, and potently inhibits Src-dependent cell proliferation with an IC50 of 100 nM. ^[1] Bosutinib significantly inhibits the proliferation of Bcr-Abl-positive leukemia cell lines KU812, K562, and MEG-01 but not Molt-4, HL-60, Ramos, and other leukemia cell lines, with IC50 of 5 nM, 20 nM and 20 nM, respectively, more potently than that of STI-571. Similar to STI-571, Bosutinib displays antiproliferative activity against the Abl-MLV-transformed fibroblasts with IC50 of 90 nM. Bosutinib ablates tyrosine phosphorylation of Bcr-Abl and STAT5 in CML cells and of v-Abl expressed in fibroblasts at the concentration of ~50 nM, 10-25 nM and 200 nM, respectively, leading to the Bcr-Abl downstream signaling inhibition of Lyn/Hck phosphorylation. ^[2] Although unable to inhibit the proliferation and survival of breast cancer cells, Bosutinib significantly decreases the motility and invasion of breast cancer cells with IC50 of ~250 nM, involved with an increase in cell-to-cell adhesion and membrane localization of β-catenin. ^[3]
Kinase Assay	The Src and Abl kinase assays
Kinase Assay	The Src kinase activity is measured in an ELISA format. Src (3 units/reaction), reaction buffer (50 mM Tris-HCl pH 7.5, 10 mM MgCl₂, 0.1 mM EGTA, 0.5 mM Na₃VO₄) and cdc2 substrate peptide are added to various concentration of Bosutinib and incubated at 30 °C for 10 minutes. The reaction is started by the addition of ATP to a final concentration of 100 μM, incubated at 30 °C for 1 hour and stopped by addition of EDTA. Instructions from the manufacturer are followed for subsequent steps. The Abl kinase assay is performed in a DELFIA solid phase europium-based detection assay format. Biotinylated peptide (2 μM) is bound to streptavidin-coated microtitration plates for 1.5 hours in 1 mg/mL ovalbumin in PBS. The plates are washed for 1 hour with PBS/0.1% Tween 80, followed by a PBS wash. The kinase reaction is incubated for 1 hour at 30°C. Abl kinase (10 units) is mixed with 50 mM Tris-HCl (pH 7.5), 10 mM MgCl₂, 80 μM EGTA, 100 μM ATP, 0.5 mM Na₃VO₄, 1% DMSO, 1 mM HEPES (pH 7.0), 200 μg/mL ovalbumin and various concentration of Bosutinib. The reaction is stopped with EDTA at a final concentration of 50 mM. The reaction is monitored with Eu-labeled phosphotyrosine antibody and DELFIA enhancement solution.
細胞実験	細胞株	Abl-MLV, Rat 2, KU812, K562, and MEG-01 cells
	濃度	Dissolved in DMSO, final concentrations ~1 μM
	反応時間	72 hours
	実験の流れ	Cells are exposed to various concentrations of Bosutinib for 72 hours. Anchorage-independent proliferation of Abl-MLV-transformed fibroblasts is measured in 96-well ultra-low binding plates treated with Sigmacote to block residual cell attachment. Cell proliferation is measured with MTS or Cell-Glo. For the determination of cell cycle or cell death, cells are prepared for FACS analysis in the CycleTest Plus DNA reagent kit and analyzed on a fluorescence-activated cell sorter flow cytometer.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	p-ABL / ABL p-FAK / FAK / p-Pyk2 / p-p130Cas / p-AKT p-Src / Src / p-c-Abl / c-Abl / p-S6 / S6 / p-ERK / ERK / p-STAT3 / STAT3		28199182
	Immunofluorescence	p-FAK / p-STAT3 / beta-catenin		18483306
	Growth inhibition assay	IC50 Cell viability		27903968

In Vivo
In Vivo	Bosutinib (60 mg/kg/day) is active against Src-transformed fibroblasts xenografts and HT29 xenografts in nude mice with T/C of 18% and 30%, respectively. ^[1] Oral administration of Bosutinib for 5 days significantly suppresses K562 tumor growth in mice in a dose-dependent manner, with the large tumors eradicated at dose of 100 mg/kg and tumor free at 150 mg/kg without overt toxicity. ^[2] As being inactive against Colo205 xenografts in nude mice at 50 mg/kg twice daily, Bosutinib dosing at 75 mg/kg twice daily is necessary against Colo205 xenografts, and increasing the dose of Bosutinib has no additional benefit, in contrast to the significant dose-dependent ability against HT29 xenografts. ^[4]
動物実験	動物モデル	Nude female mice injected with K562 cells
	投与量	~150 mg/kg/day
	投与経路	Oral gavage

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT05363488	Completed	Myeloid Leukemia	Pfizer	October 8 2021	--
NCT04258943	Active not recruiting	Philadelphia Chromosome Positive CML\|Accelerated Phase Chronic Myelogenous Leukemia\|Blastic Phase Chronic Myelogenous Leukemia\|Chronic Phase Chronic Myelogenous Leukemia	Children''s Oncology Group\|Erasmus Medical Center\|Dutch Childhood Oncology Group\|Innovative Therapies for Children with Cancer\|Pfizer	April 6 2020	Phase 1\|Phase 2
NCT03023319	Completed	Carcinoma Non-Small-Cell Lung\|Mesothelioma\|Bladder Cancer\|Ovarian Cancer\|Peritoneal Cancer\|Thymoma\|Thymus Cancer\|Uterine Cervical Cancer	Nagla Abdel Karim\|Augusta University	December 10 2019	Phase 1
NCT03888222	Completed	Dementia With Lewy Bodies	Georgetown University\|Alzheimer''s Association	April 23 2019	Phase 2
NCT03854903	Active not recruiting	Metastatic Breast Cancer\|Human Epidermal Growth Factor 2 Negative Carcinoma of Breast\|Hormone Receptor Positive Breast Cancer	Georgetown University\|Pfizer	April 1 2019	Phase 1

参考
[1] Boschelli DH, et al. J Med Chem, 2001, 44(23), 3965-3977. [2] Golas JM, et al. Cancer Res, 2003, 63(2), 375-381. [3] Vultur A, et al. Mol Cancer Ther, 2008, 7(5), 1185-1194. [4] Golas JM, et al. Cancer Res, 2005, 65(12), 5358-5364. [5] Redaelli S, et al. Leukemia, 2010, 24(6), 1223-1227. [6] Sakuma Y, et al. Oncol Rep, 2011, 25(3), 661-667. [7] Shayahati Bieerkehazhi, et al. Oncotarget. 2017 Jan 3;8(1):1469-1480. + 展開

参考

+ 展開

化学情報

分子量	530.45	化学式	C₂₆H₂₉Cl₂N₅O₃
CAS No.	380843-75-4	SDF	Download Bosutinib SDFをダウンロードする
Smiles	CN1CCN(CC1)CCCOC2=C(C=C3C(=C2)N=CC(=C3NC4=CC(=C(C=C4Cl)Cl)OC)C#N)OC
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 : 100 mg/mL ( (188.51 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。)

Water : Insoluble

Ethanol : 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
	Clear solution	1%DMSO 1 40%PEG300 Click to order 2 5%Tween 80 Click to order 3 54%ddH2O	0.625mg/ml (1.18mM)	Taking the 1 mL working solution as an example, add 10 μL of 62.5 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 540 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.	投与溶液組成計算機
Clear solution	5% DMSO 1 95% Corn oil	0.65mg/ml (1.23mM)	Taking the 1 mL working solution as an example, add 50 μL of 13 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG300 Click to order 2 5%Tween 80 Click to order 3 50%ddH2O	5.0mg/ml (9.43mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

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

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

* 必須

* 大学・企業名 大学・企業名を記入してください

* 名前 名前を記入してください

* 電子メール 電子メール・アドレスを記入してください 有効なメールアドレスを入力してください

電話番号

* 内容 お問い合わせ内容をご入力ください

よくある質問（FAQ）

質問1:
Can I give S1014 Bosutinib to mice by oral gavage? If so, how to dissolve the drug?

回答
For oral gavage, S1014 Bosutinib can be dissolved in 5% Tween 80+0.5% CMC Na at 30 mg/ml as a suspension.

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):