Fostamatinib disodium hexahydrate

製品コードS4944 バッチS494401

化学情報

	Synonyms	Tavalisse, R788 disodium hexahydrate, Tamatinib Fosdium hexahydrate	Storage (From the date of receipt)	3 years -20°C powder
	化学式	C₂₃H₃₆FN₆Na₂O₁₅P
	分子量	732.51	CAS No.	914295-16-2
Solubility (25°C)*	体外	DMSO	100 mg/mL (136.51 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <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	Fostamatinib (R788) disodium (Tamatinib Fosdium) hexahydrate, a prodrug of the active metabolite R406, is a Syk inhibitor with IC50 of 41 nM in a cell-free assay.
in vitro	R788 is a prodrug of the spleen tyrosine kinase (Syk) inhibitor R406. R788 is a competitive inhibitor for ATP binding with a Ki 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]
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]

プロトコル(参考用のみ)

キナーゼアッセイ	Fluorescence polarization kinase assay and Ki determination
キナーゼアッセイ	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 K_m and V_max. Finally the apparent K_m (or apparent K_i/V_max) is plotted against the inhibitor concentration to determine the K_i.
細胞アッセイ	細胞株	Cultured human mast cells (CHMC)
	濃度	0-100 μM
	反応時間	0.5 h
	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.
動物実験	動物モデル	Balb/c mice with arthritis
	投薬量	1 mg/kg or 5 mg/kg
	投与方法	o.g.

参考

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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：

C-type lectin-like receptor 2 specifies a functionally distinct subpopulation within phenotypically defined hematopoietic stem cell population that contribute to emergent megakaryopoiesis [ Int J Hematol, 2022, 10.1007/s12185-021-03220-9]	PubMed: 35106701
Optimizing drug inhibition of IgE-mediated anaphylaxis in mice [ J Allergy Clin Immunol, 2021, S0091-6749(21)00979-9]	PubMed: 34186142
Effects of Inhibitors against Syk-BTK-PI3K Signaling on Platelet Function [ ScholarsArchive@OSU, 2020, None]	PubMed: None

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。

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