Fostamatinib (R788)

製品コード：S2625 純度：99.59%

Fostamatinib (R788), a prodrug of the active metabolite R406, is a Syk inhibitor with IC50 of 41 nM, strongly inhibits Syk but not Lyn, 5-fold less potent to Flt3. Phase 3.

CAS No. 901119-35-5

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 55500	国内在庫あり
2mg	JPY 40500	国内在庫あり
5mg	JPY 70500	国内在庫あり
10mg	JPY 130500	国内在庫あり
100mg	JPY 445500	国内在庫あり
1g	JPY 1048500	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（38）

製品安全説明書

現在のバッチを見る：純度： 99.59%

99.59

Fostamatinib (R788)関連製品

関連ターゲット	ZAP70	もっと見る
関連製品	R406 R406 (free base) PRT062607 (P505-15) HCl Entospletinib (GS-9973) Piceatannol BAY-61-3606 PRT-060318 2HCl TAK-659 Hydrochloride RO9021	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

Sykシグナル伝達経路

Syk阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
human Ramos cells	Function assay			Inhibition of SYK in human Ramos cells, IC50=0.267 μM	23350847
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

Fostamatinib (R788), a prodrug of the active metabolite R406, is a Syk inhibitor with IC50 of 41 nM, strongly inhibits Syk but not Lyn, 5-fold less potent to Flt3. Phase 3.

特性

Converted into its active metabolite R406 in vivo.

Targets

Syk ^[1]	Adenosine A3 receptor ^[1]	Adenosine transporter ^[1]	Monoamine transporter ^[1]
41 nM	81 nM	1.84 μM	2.74 μM

In Vitro
In vitro	R788 is a prodrug of the spleen tyrosine kinase (Syk) inhibitor R406. R788 is a competitive inhibitor for ATP binding with a K_i of 30 nM. R788 dose-dependently inhibits anti-IgE-mediated CHMC degranulation with an EC50 of 56 nM. R788 also inhibits the anti-IgE-induced production and release of LTC4 and cytokines and chemokines, including TNFα, IL-8, and GM-CSF. Inhibition of Syk by R788 results in inhibition of all phosphorylation events downstream of Syk signaling. Next to FcϵRI signaling in CHMC, R788 most potently inhibits the signaling of IL-4 and IL-2 receptors. R788 specifically inhibits FcγR signaling in human mast cells, macrophages, and neutrophils. R788 can inhibit local inflammatory injury mediated by immune complexes. ^[1] R788 induces apoptosis of the majority of examined DLBCL cell lines. In R788-sensitive DLBCL cell lines, R788 specifically inhibits both tonic- and ligand-induced BCR signaling (autophosphorylation of SYK525/526 and SYK-dependent phosphorylation of the B-cell linker protein [BLNK]). ^[2]
Kinase Assay	Fluorescence polarization kinase assay and K_i determination
Kinase Assay	The fluorescence polarization reactions are performed. For K_i determination, duplicate 200-μL reactions are set up at eight different ATP concentrations from 200 μM (2-fold serial dilutions) in the presence of either DMSO or R788 at 125, 62.5, 31.25, 15.5, or 7.8 nM. At different time points, 20 μL of each reaction is removed and quenched to stop the reaction. For each concentration of R788, the rate of reaction at each concentration of ATP is determined and plotted against the ATP concentration to determine the apparent Km and V_max (maximal rate). Finally the apparent K_m (or apparent K_i/V_max) is plotted against the inhibitor concentration to determine the K_i.
細胞実験	細胞株	Cultured human mast cells (CHMC)
	濃度	0 μM -100 μM
	反応時間	30 minutes
	実験の流れ	Cultured human mast cells (CHMC) are derived from cord blood CD34⁺ progenitor cells and grown, primed, and stimulated and shown in supplemental data. Before stimulation, cells are incubated with R788 or DMSO for 30 minutes. Cells are then stimulated with either 0.25 to 2 mg/mL anti-IgE or anti-IgG or 2 μM ionomycin. For tryptase measurement, ∼1500 cells per well are stimulated for 30 min in modified Tyrode's buffer. For LTC4 and cytokine production, 100,000 cells per well are stimulated for 1 or 7 hours, respectively. Tryptase activity is measured by luminescence readout of a peptide substrate, and LTC4 and cytokines are measured using Luminex multiplex technology.

In Vivo
In Vivo	Oral administration of R788 to mice reduces immune complex-mediated inflammation in a reverse-passive Arthus reaction and two antibody-induced arthritis models. ^[1] In another study, R788 effectively inhibits BCR signaling in vivo, resulting in reduced proliferation and survival of the malignant B cells and significantly prolongs survival of the treated animals. ^[3] R788 demonstrates a significant reduction in major inflammatory mediators such as TNFalpha, IL-1, IL-6 and IL-18, leading to reduced inflammation and bone degradation in models of rheumatoid arthritis. ^[4]
動物実験	動物モデル	Balb/c mice with arthritis
	投与量	1 mg/kg or 5 mg/kg
	投与経路	Orally b.i.d

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT05904093	Not yet recruiting	Sickle Cell Disease\|Hb-SS Disease\|Hemoglobin S\|Disease Sickle Cell Anemia\|Sickle Cell Disorders\|Hemoglobin Beta Thalassemia Disease	National Heart Lung and Blood Institute (NHLBI)\|National Institutes of Health Clinical Center (CC)	May 15 2024	Phase 1
NCT05509582	Enrolling by invitation	Immune Mediated Anemia\|Immune Mediated Thrombocytopenia\|Chronic GVHD	National Heart Lung and Blood Institute (NHLBI)\|National Institutes of Health Clinical Center (CC)	May 15 2024	Phase 2
NCT06071520	Completed	Primary Immune Thrombocytopenia	Fundación Pública Andaluza para la gestión de la Investigación en Sevilla	March 1 2023	--
NCT05613296	Not yet recruiting	ITP - Immune Thrombocytopenia\|Chronic ITP\|Refractory ITP	Gruppo Italiano Malattie EMatologiche dell''Adulto	February 2023	--
NCT04543279	Terminated	Myelofibrosis\|Thrombocytopenia	Washington University School of Medicine\|Rigel Pharmaceuticals	May 3 2021	Phase 2
NCT04904276	Terminated	ITP\|Immune Thrombocytopenia	Rigel Pharmaceuticals	May 18 2021	--

参考
[1] Braselmann S, et al. J Pharmacol Exp Ther, 2006, 319(3), 998-1008. [2] Chen L et al.Blood, 2008, 111(4), 2230-2237. [3] Suljagic M, et al. Blood, 2010, 116(23), 4894-4905. [4] Bajpai M. IDrugs, 2009, 12(3), 174-185. + 展開

参考

[4] Bajpai M. IDrugs, 2009, 12(3), 174-185.

+ 展開

化学情報

分子量	580.46	化学式	C₂₃H₂₆FN₆O₉P
CAS No.	901119-35-5	SDF	Download Fostamatinib (R788) SDFをダウンロードする
Smiles	CC1(C(=O)N(C2=C(O1)C=CC(=N2)NC3=NC(=NC=C3F)NC4=CC(=C(C(=C4)OC)OC)OC)COP(=O)(O)O)C
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 : 116 mg/mL ( (199.84 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

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:
What’s the difference between S2625 and S2206?

回答
S2206 is more stable than S2625. The water solubility of S2206 is better than S2625. The absorption of S2206 is harder than S2625, so you need to test the suitable dosage if you use the product in animal assays. The potency of S2206 and S2625 is similar.

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