AS-604850

製品コードS2681 バッチS268101

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₁H₅F₂NO₄S
	分子量	285.22	CAS No.	648449-76-7
Solubility (25°C)*	体外	DMSO	57 mg/mL (199.84 mM)
		Ethanol	5 mg/mL (17.53 mM)
		Water	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	AS-604850 is a selective, ATP-competitive PI3Kγ inhibitor with IC50 of 250 nM, over 80-fold selectivity for PI3Kγ than PI3Kδ/β, and 18-fold more selective for PI3Kγ than PI3Kα.
in vitro	AS-604850 is ATP-competitive PI3Kγ inhibitor with K_i values of 0.18 μM. AS-604850 is isoform selective inhibitor of PI3Kγ with over 30-fold selectivity for PI3Kδ and β, and 18-fold selectivity over PI3Kα. (PI3Kα: IC50 = 4.5 μM, PI3Kγ and β: IC50 > 20μM) AS-604850 is capable of inhibiting C5a-mediated PKB phosphorylation in RAW264 mouse macrophages with an IC50 with 10 μM. AS-604850 blocks MCP-1-mediated chemotaxis in Pik3cg ^+/+ monocytes in a concentration- dependent manner, with an IC50 of 21 mM, but dosn't affect chemotaxis in Pik3cg^-/- cells, indicating that AS-604850 acts through PI3Kγ. ^[1] AS-604850 diminishes glycochenodeoxycholate (GCDC) induced Akt-phosphorylation and apoptosis in rat hepatocytes. AS-604850 diminishes bile salt-induced apoptosis in HepG2 Ntcp and Huh7-Ntcp cells. ^[2] AS604850 causes a concentration-dependent suppression of chemotactic responses of EoL-1 cells and blood eosinophils to platelet-activating factor (PAF). ^[3]
in vivo	AS-604850 reduces RANTES-induced peritoneal neutrophil recruitment with a ED50 of 42.4 mg/kg. In the thioglycollate-induced peritonitis model, oral administration of 10 mg/kg AS-604850 results in a 31% reduction of neutrophil recruitment. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	In vitro PI3Kγ Kinase Assay
キナーゼアッセイ	Human PI3Kγ (100 ng) is incubated at RT with kinase buffer (10 mM MgCl₂, 1 mM β-glycerophosphate, 1 mM DTT, 0.1 mM Na₃VO₄, 0.1% Na Cholate and 15 M ATP/100 nCi γ[³³]ATP, final concentrations) and lipid vesicles containing 18 M PtdIns and 250 M of PtdSer (final concentrations), in the presence of AS-252424 or DMSO. Kinase reaction is stopped by adding 250 g of Neomycin-coated Scintillation Proximity Assay (SPA) beads and preceded.
細胞アッセイ	細胞株	HepG2 Ntcp and Huh7-Ntcp cells
	濃度	2.5 μM
	反応時間	2 - 4 hours
	実験の流れ	Hepatocyte cultures are treated with diluent (DMSO), 25 μM TLC, 250 μM TCDC, 50 μM GCDC, or 50 ng/ml Fas for 2-4 hours HepG2-Ntcp and Huh7-Ntcp cells are treated with DMSO, 20 μM TLC, 75 μM TCDC or GCDC, 200 μM etoposide or 200 ng/ml TNFa plus 28 ng/ml actinomycin D for 2-4 hours. The number of apoptotic cells is determined morphologically using fluorescent staining and expressed as % of cells. Apoptosis is confirmed in human cell lines by determination of caspase-3/-7 activity and in rat hepatocytes by detection of the 17 kDa proteolytic cleavage fragment of caspase-3 by immunoblotting; equal protein loading is monitored by immunoblotting for actin.
動物実験	動物モデル	RANTES (0.5 mg/kg in 200 ml saline) or thioglycollate (40 ml/kg) are intraperitoneally injected to C3H mice to induce peritonitis mouse models
	投薬量	0, 1, 3, 10 or 30 mg/kg for RANTES, 10 mg/kg for thioglycollate
	投与方法	Oral administration 30 or 15 minutes before injection of RANTES or thioglycollate

参考

カスタマーフィードバック

: Data from [Data independently produced by J Biol Chem, 2014, 289(46), 32109-20]

: , , Dr. Zhang of Tianjin Medical University

: Data from [Data independently produced by , , Nature, 2017, 542(7642):489-493]

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：

GLP-1 and GIP receptors signal through distinct β-arrestin 2-dependent pathways to regulate pancreatic β cell function [ Cell Rep, 2023, 10.1016/j.celrep.2023.113326]	PubMed: 37897727
DOCK2 and phosphoinositide-3 kinase δ mediate two complementary signaling pathways for CXCR5-dependent B cell migration [ Front Immunol, 2022, 13:982383]	PubMed: 36341455
Repressing MYC by targeting BET synergizes with selective inhibition of PI3Kα against B cell lymphoma [ Cancer Lett, 2021, S0304-3835(21)00532-2]	PubMed: 34688842
Topical Application of the PI3Kβ-Selective Small Molecule Inhibitor TGX-221 Is an Effective Treatment Option for Experimental Epidermolysis Bullosa Acquisita [ Front Med (Lausanne), 2021, 8:713312]	PubMed: 34557502
Topical Application of the PI3Kβ-Selective Small Molecule Inhibitor TGX-221 Is an Effective Treatment Option for Experimental Epidermolysis Bullosa Acquisita [ Front Med (Lausanne), 2021, 8:713312]	PubMed: 34557502
Mussel-inspired injectable hydrogel and its counterpart for actuating proliferation and neuronal differentiation of retinal progenitor cells [ Biomaterials, 2019, 194:57-72]	PubMed: 30583149
Recruitment of Vps34 PI3K and enrichment of PI3P phosphoinositide in the viral replication compartment is crucial for replication of a positive-strand RNA virus [ PLoS Pathog, 2019, 15(1):e1007530]	PubMed: 30625229
PI3Kβ links integrin activation and PI(3,4)P2 production during invadopodial maturation. [ Mol Biol Cell, 2019, 30(18):2367-2376]	PubMed: 31318314
Phosphatidylinositol 3-kinase δ Blockade Increases Genomic Instability in B Cells [ Nature, 2017, 23;542(7642):489-493.]	PubMed: 28199309
Phosphatidylinositol 3-kinase δ blockade increases genomic instability in B cells. [Compagno M, et al. Nature, 2017, 542(7642):489-493]	PubMed: 28199309

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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