Sunitinib malate

別名：SU11248 malate

製品コード：S1042 純度：99.60%

Sunitinib malate is a multi-targeted RTK inhibitor targeting VEGFR2 (Flk-1) and PDGFRβ with IC50 of 80 nM and 2 nM in cell-free assays, and also inhibits c-Kit. Sunitinib Malate effectively inhibits autophosphorylation of Ire1α. Sunitinib Malate increases both death receptor and mitochondrial-dependent apoptosis.

CAS No. 341031-54-7

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 28600	国内在庫あり
10mg	JPY 11500	国内在庫あり
50mg	JPY 14500	国内在庫あり
100mg	JPY 22000	国内在庫あり
500mg	JPY 67000	国内在庫あり
1g	JPY 104500	国内在庫あり

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（166）

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製品安全説明書

現在のバッチを見る：純度： 99.60%

99.60

Sunitinib malate関連製品

関連ターゲット	PDGFRα PDGFRβ	もっと見る
関連製品	Crenolanib CP-673451 Orantinib (SU6668) Tyrphostin AG 1296 Trapidil PP121 AZD2932	もっと見る
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

PDGFRシグナル伝達経路

PDGFR阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
U251	Kinase Assay	10 μM	1 h	Inhibition of VEGFR2 with IC50 of 0.0189 μM	24890652
SH-SY5Y	Kinase Assay	10 μM	1 h	Inhibition of PDGFRbeta with IC50 of 0.0831 μM	24890652
A431	Kinase Assay	10 μM	1 h	Inhibition of EGFR with IC50 of 0.1721 μM	24890652
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

IRE1α ^[7]	Kit ^[1] (Cell-free assay)	FLT3 ^[1] (Cell-free assay)	PDGFRβ ^[1] (Cell-free assay)	VEGFR2 ^[1] (Cell-free assay)
			2 nM	80 nM

In Vitro
In vitro	Sunitinib also potently inhibits Kit and FLT-3. ^[1] Sunitinib is a potent ATP-competitive inhibitor of VEGFR2 (Flk1) and PDGFRβ with K_i of 9 nM and 8 nM, respectively, displaying >10-fold higher selectivity for VEGFR2 and PDGFR than FGFR-1, EGFR, Cdk2, Met, IGFR-1, Abl, and src. In serum-starved NIH-3T3 cells expressing VEGFR2 or PDGFRβ, Sunitinib inhibits VEGF-dependent VEGFR2 phosphorylation and PDGF-dependent PDGFRβ phosphorylation with IC50 of 10 nM and 10 nM, respectively. Sunitinib inhibits VEGF-induced proliferation of serum-starved HUVECs with IC50 of 40 nM, and inhibits PDGF-induced proliferation of NIH-3T3 cells overexpressing PDGFRβ or PDGFRα with IC50 of 39 nM and 69 nM, respectively. ^[2] Sunitinib inhibits phosphorylation of wild-type FLT3, FLT3-ITD, and FLT3-Asp835 with IC50 of 250 nM, 50 nM, and 30 nM, respectively. Sunitinib inhibits the proliferation of MV4;11 and OC1-AML5 cells with IC50 of 8 nM and 14 nM, respectively, and induces apoptosis in a dose-dependent manner. ^[3]
Kinase Assay	Biochemical Tyrosine Kinase Assays
Kinase Assay	IC50 values for Sunitinib against VEGFR2 (Flk-1) and PDGFRβ are determined using glutathione S-transferasefusion proteins containing the complete cytoplasmic domain of the RTK. Biochemical tyrosine kinase assays to quantitate the trans-phosphorylation activity of VEGFR2 (Flk-1) and PDGFRβ are performed in 96-well microtiter plates precoated (20 μg/well in PBS; incubated overnight at 4 °C) with the peptide substrate poly-Glu,Tyr (4:1). Excess protein binding sites are blocked with the addition of 1-5% (w/v) BSA in PBS. Purified GST-fusion proteins are produced in baculovirus-infected insect cells. GST-VEGFR2 and GST-PDGFRβ are then added to the microtiter wells in 2 × concentration kinase dilution buffer consisting of 100 mM HEPES, 50 mM NaCl, 40 μM NaVO₄, and 0.02% (w/v) BSA. The final enzyme concentration for GST-VEGFR2 or GST-PDGFRβ is 50 ng/mL. Twenty-five μL of diluted Sunitinib are subsequently added to each reaction well to produce a range of inhibitor concentrations appropriate for each enzyme. The kinase reaction is initiated by the addition of different concentrations of ATP in a solution of MnCl₂ so that the final ATP concentrations spanned the Km for the enzyme, and the final concentration of MnCl₂ is 10 mM. The plates are incubated for 5-15 minutes at room temperature before stopping the reaction with the addition of EDTA. The plates are then washed three times with TBST. Rabbit polyclonal antiphosphotyrosine antisera are added to the wells at a 1:10,000 dilution in TBST containing 0.5% (w/v) BSA, 0.025% (w/v) nonfat dry milk, and 100 μM NaVO₄ and incubated for 1 hour at 37 °C. The plates are then washed three times with TBST, followed by the addition of goat antirabbit antisera conjugated with horseradish peroxidase (1:10,000 dilution in TBST). The plates are incubated for 1 hour at 37 °C and then washed three times with TBST. The amount of phosphotyrosine in each well is quantitated after the addition of 2,2′-azino-di-[3-ethylbenzthiazoline sulfonate] as substrate.
細胞実験	細胞株	RS4;11, MV4;11, and OC1-AML5
	濃度	Dissolved in DMSO, final concentrations ~10 μM
	反応時間	24 and 48 hours
	実験の流れ	Cells are starved overnight in medium containing 0.1% FBS prior to addition of Sunitinib and FL (50 ng/mL; FLT3-WT cells only). Proliferation is measured after 48 hours of culture using the Alamar Blue assay or trypan blue cell viability assays. Apoptosis is measured 24 hours after Sunitinib addition by Western blotting to detect cleavage of poly (ADP-ribose) polymerase (PARP) or levels of caspase-3.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	p-STAT3 / STAT3 / p-Src / Src / p-AKT / AKT / p-ERK / ERK p-GSK3β / GSK3β / MYCN p-AKT / AKT / p-ERK / ERK		19244102
	Growth inhibition assay	Cell viability		24369536

In Vivo
In Vivo	Consistent with the substantial and selective inhibition of VEGFR2 or PDGFR phosphorylation and signaling in vivo, Sunitinib (20-80 mg/kg/day) exhibits broad and potent dose-dependent anti-tumor activity against a variety of tumor xenograft models including HT-29, A431, Colo205, H-460, SF763T, C6, A375, or MDA-MB-435. Sunitinib dosing at 80 mg/kg/day for 21 days leads to complete tumor regression in six of eight mice, without tumor re-growing during a 110-day observation period after the end of treatment. Second round of treatment with Sunitinib remains efficacious against tumors that are not fully regressed during the first round of treatment. Sunitinib treatment results in significant decrease in tumor MVD, with ~40% reduction in SF763T glioma tumors. SU11248 treatment results in a complete inhibition of additional tumor growth of luciferase-expressing PC-3M xenografts, despite no reduction in tumor size. ^[2] Sunitinib treatment (20 mg/kg/day) dramatically suppresses the growth subcutaneous MV4;11 (FLT3-ITD) xenografts and prolongs survival in the FLT3-ITD bone marrow engraftment model. ^[3]
動物実験	動物モデル	Female nu/nu mice implanted s.c. with HT-29, A431, Colo205, H-460, SF763T, C6, A375, or MDA-MB-435, and male nu/nu mice bearing luciferase-expressing PC-3M tumors
	投与量	~80 mg/kg
	投与経路	Orally once daily

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT06222593	Not yet recruiting	Carcinoma Renal Cell	State University of New York at Buffalo	June 1 2024	Phase 1\|Phase 2
NCT06208748	Not yet recruiting	Gastrointestinal Stromal Tumors\|GIST	Sarcoma Alliance for Research through Collaboration\|Cogent Biosciences Inc.\|Dana-Farber Cancer Institute\|The Life Raft Group	March 2024	Phase 2
NCT05745142	Completed	Carcinoma Renal Cell\|Clear-cell Metastatic Renal Cell Carcinoma	Pfizer	February 23 2023	--
NCT05043090	Recruiting	Papillary Renal Cell Carcinoma	AstraZeneca	October 28 2021	Phase 3
NCT04669366	Completed	Kidney Neoplasms	Pfizer	January 20 2021	--

参考
[1] Sun L, et al. J Med Chem, 2003, 46(7), 1116-1119. [2] Mendel DB, et al. Clin Cancer Res, 2003, 9(1), 327-337. [3] Anne-Marie O'Farrell, et al. Blood . 2003 May 1;101(9):3597-605. [4] Abrams TJ, et al. Mol Cancer Ther, 2003, 2(10), 1011-1021. [5] Yee KW, et al. Blood, 2004, 104(13), 4202-4209. [6] Ikezoe T, et al. Mol Cancer Ther, 2006, 5(10), 2522-2530. [7] Maruf M U Ali, et al. EMBO J . 2011 Mar 2;30(5):894-905. + 展開

参考

+ 展開

化学情報

分子量	532.56	化学式	C₂₂H₂₇FN₄O₂.C₄H₆O₅
CAS No.	341031-54-7	SDF	Download Sunitinib malate SDFをダウンロードする
Smiles	CCN(CC)CCNC(=O)C1=C(NC(=C1C)C=C2C3=C(C=CC(=C3)F)NC2=O)C.C(C(C(=O)O)O)C(=O)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 : 70 mg/mL ( (131.44 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

5%DMSO 1 Corn oil

5.0mg/ml (9.39mM)

Taking the 1 mL working solution as an example, add 50 μL of 100 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.

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。

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よくある質問（FAQ）

質問1:
I was wondering that the compound is in its cis or trans form?

回答
S1042 Sunitinib Malate is Z form.

質問2:
What is the difference between Sunitinib Malate(S1042) and Sunitinib(S7781)?

回答
S1042 is the Malate salt form of Sunitinib. The biological activities of these two compounds are the same but the solubility of these two compounds in aqueous solvent are different.

C1=C0/X	C1:	LOG(C1):
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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):