1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERIPA-56Cat. No.: HY-101032CAS No.: 1956370-21-0分式: CHNO分量: 221.3作靶點: RIP kinase作通路: Apoptosis儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數據體外實驗 DMSO : 100 mg/mL (451.88 mM)* means soluble, but satura

2、tion unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 4.5188 mL 22.5938 mL 45.1875 mL5 mM 0.9038 mL 4.5188 mL 9.0375 mL10 mM 0.4519 mL 2.2594 mL 4.5188 mL請根據產品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內實驗請根據您的實驗動物和給藥式選擇適當的溶解案，配制前請先配制澄的儲備液，再依次添加助溶劑(為保證實驗結果的可靠性，體內實驗的作液，建議您現現配，當天使；澄的儲備液可以根據儲存條件

3、，適當保存；以下溶劑前的百分指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (11.30 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (11.30 mM); Clear solution3. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/2 Master of Small Molecules 您邊

4、的抑制劑師www.MedChemESolubility: 2.5 mg/mL (11.30 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 RIPA-56種效選擇和代謝穩定的受體相互作蛋 1 (RIP1) 抑制劑，IC50 為 13 nM。RIPA-56 可于治療全炎癥反應綜合征 1。IC50 & Target IC50: 13 nM (RIP1) 1體外研究 RIPA-56 shows efficient inhibition of RIP1 kinase activity, with an IC50 of 13 nM and no inhibition

5、of RIP3kinase activity at a 10 M concentration. RIPA-56 also demonstrates potency in protection of murine L929cells from TNF/z-VAD-FMK (TZ)-induced necrosis (EC50=27 nM) 1.體內研究 In the SIRS mice disease model, RIPA-56 efficiently reduces tumor necrosis factor alpha (TNF)-inducedmortality and multi-or

6、gan damage. Compared to known RIP1 inhibitors, RIPA-56 is potent in both human andmurine cells, is much more stable in vivo, and is efficacious in animal model studies. RIPA-56 has animpressive PK profile in mice with a 3.1 h half-life, 22% oral bioavailability (P.O.), and 100% bioavailabilityfrom i

7、ntraperitoneal injection (I.P.) 1.PROTOCOLCell Assay 1 Cell necrosis assay is performed in 96-well cell culture plate. 3,000 cells are plated in each well and culturedat 37C overnight. HT-29 cells are treated with 20 ng/mL TNF/100 nM Smac Mimetics/20 M z-VAD-FMKand RIPA-56 for 24 h. L929 cells are t

8、reated with 20 ng/mL TNF/20 M z-VAD-FMK and RIPA-56 for 6 h.The cell survival ratio is determined using the Cell Titer-Glo Luminescent Cell Viability Assay kit 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: Following intraveneous (IV), i

9、ntraperitoneal (IP), or oral administration (PO) of RIPA-56 to C57BL/6Administration 1 mice (n=3), blood is sampled through eye puncture at various time points. Compound concentrations in theplasma samples are analyzed by LCMS/MS. Pharmacokinetic parameters are determined from individualanimal data

10、using noncompartmental analysis in phoenix 64 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Ren Y, et al. Discovery of a Highly Potent, Selective, and Metabolically Stable Inhibitor of Receptor-InteractingProtein 1 (RIP1) for theTreatment of Systemic Inflammatory Response Syndrome. J Med Chem. 2017 Feb 9;60(3):972-986.McePdfHeightCaution: Product has not been fully