RIPA-56-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERIPA-56Cat. No.: HY-101032CAS No.: 1956370-21-0分式: CHNO分量: 221.3作靶点: RIP kinase作通路: Apoptosis储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (451.88 mM)* means soluble, but satura

2、tion unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液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请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄的储备液可以根据储存条件

3、，适当保存；以下溶剂前的百分指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (11.30 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (11.30 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/2 Master of Small Molecules 您边

4、的抑制剂师www.MedChemESolubility: 2.5 mg/mL (11.30 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 RIPA-56种效选择和代谢稳定的受体相互作蛋 1 (RIP1) 抑制剂，IC50 为 13 nM。RIPA-56 可于治疗全炎症反应综合征 1。IC50 & Target IC50: 13 nM (RIP1) 1体外研究 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.体内研究 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