HS-1371

製品コードS8775 バッチS877501

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder
	化学式	C₂₄H₂₄N₄O
	分子量	384.47	CAS No.	2158197-70-5
Solubility (25°C)*	体外	DMSO	13 mg/mL (33.81 mM)
		Ethanol	4 mg/mL (10.4 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	HS-1371 is a potent RIP3 kinase inhibitor with an IC50 of 20.8 nM. It binds to the ATP binding pocket of RIP3 and inhibits ATP binding to prevent RIP3 enzymatic activity in vitro.
in vitro	HS-1371 shows an inhibitory effect on S227 auto-phosphorylation of RIP3 at the basal level. It displays a complete inhibitory effect on TNF-induced necroptosis signaling, showing no phosphorylation of RIP3 and MLKL in HT-29 cells. Inhibition of RIP3 kinase activity by HS-1371 blocks necrosome complex formation, showing disruption of MLKL recruitment. HS-1371 rescues cells from TNF-induced necroptosis. It rescues cells from RIP3-dependent necroptotic cell death but not apoptotic cell death^[1].

製品説明

HS-1371 is a potent RIP3 kinase inhibitor with an IC50 of 20.8 nM. It binds to the ATP binding pocket of RIP3 and inhibits ATP binding to prevent RIP3 enzymatic activity in vitro.

in vitro

HS-1371 shows an inhibitory effect on S227 auto-phosphorylation of RIP3 at the basal level. It displays a complete inhibitory effect on TNF-induced necroptosis signaling, showing no phosphorylation of RIP3 and MLKL in HT-29 cells. Inhibition of RIP3 kinase activity by HS-1371 blocks necrosome complex formation, showing disruption of MLKL recruitment. HS-1371 rescues cells from TNF-induced necroptosis. It rescues cells from RIP3-dependent necroptotic cell death but not apoptotic cell death^[1].

プロトコル(参考用のみ)

キナーゼアッセイ	Enzymatic assays
キナーゼアッセイ	The inhibitory activities of all compounds toward RIP3 were measured by Reaction Biology Corp by means of radiometric kinase assays ([γ-32P]ATP). The enzymatic activity of RIP3 was monitored using 20 μM of myelin basic protein (MBP) dissolved in freshly prepared reaction buffer (20 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% BRIJ-35, 0.02 mg/mL BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO). Each putative RIP3 inhibitor was dissolved in 100% DMSO at specific concentrations and serially diluted with epMotion 5070 in DMSO. Human RIP3 and 20 μM of peptide substrate (MBP) were added to the reaction buffer. After delivering the candidate inhibitor dissolved in DMSO to the kinase reaction mixture using Acoustic technology (Echo550; nanoliter range), the reaction mixture was incubated for 20 min at room temperature. To initiate the enzymatic reaction, 33P-ATP with specific activity of 10 μCi/μL was added to the reaction mixture to reach a final ATP concentration of 10 μM. Radioactivity was then monitored using the filter binding method after incubation of the reaction mixture for 2 h at room temperature. At given concentrations of inhibitor, biochemical potency was measured by the percent remaining kinase activity with respect to the vehicle (dimethyl sulfoxide) reaction. Curve fits and IC50 values were then obtained using the PRISM program. The ATP-competitive inhibitor staurosporine (STSP) was employed as a positive control in this study because of its high biochemical potency against various kinases including RIP3.
細胞アッセイ	細胞株	HT-29 cells
	濃度	5 μM
	反応時間	2 h
	実験の流れ	HT-29 cells were pretreated with Nec-1 (40 μM), DAB (5 μM) or HS-1371 (5 μM) for 2 h and then treated with TSZ for 4 h. Cell lysates were immunoprecipitated with anti-RIP3 antibody.

参考

[1] Park HH, et al. Exp Mol Med. 2018, 50(9):125.

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：

Necroptotic virotherapy of oncolytic alphavirus M1 cooperated with Doxorubicin displays promising therapeutic efficacy in TNBC [ Oncogene, 2021, 10.1038/s41388-021-01869-4]	PubMed: 34155344

Necroptotic virotherapy of oncolytic alphavirus M1 cooperated with Doxorubicin displays promising therapeutic efficacy in TNBC [ Oncogene, 2021, 10.1038/s41388-021-01869-4]

PubMed: 34155344

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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