GSK2982772 - RIPK1 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGSK2982772Cat. No.: HY-101760CAS No.: 1622848-92-3分式: CHNO分量: 377.4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 (264.97 mM)* means soluble, but sat

2、uration unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.6497 mL 13.2485 mL 26.4971 mL5 mM 0.5299 mL 2.6497 mL 5.2994 mL10 mM 0.2650 mL 1.3249 mL 2.6497 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，配制前请先配制澄清的储备液，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；澄清的储备液可以根

3、据储存条件，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 (6.62 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 (6.62 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/2 Master of Small Molecule

4、s 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (6.62 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 GSK2982772可服的、有效的ATP竞争型的RIP1酶抑制剂，对和猴 RIP1 的IC50值分别为16 nM 和 20nM。IC50 & Target IC50: 16 nM (human RIP1 FP), 20 nM (monkey RIP1 FP), 2 M (rat RIP1 FP), 2.5 M (mouse RIP1 FP) 1体外研究 GSK2982772 shows more than 1,00

5、0-fold selectivity for ERK5 over a panel of over 339 kinases at 10 M. Instimulated cellular systems,GSK2982772 is also able to reduce spontaneous production of cytokines (IL-1and IL-6) in a concentration-dependent fashion from ulcerative colitis explant tissue in overnight incubations.GSK2982772 pro

6、duces a weak concentration dependent inhibition of hERG in human embryonic kidney(HEK-293) cells, with an estimated IC50 of 195 M, and also shows a weak activation of the humanPregnane X receptor (hPXR) with an EC50 of 13 M 1.体内研究 GSK2982772 is dosed orally 15 min prior to TNF and shows 68, 80, and

7、87% protection from temperatureloss over 6 h, at doses of 3, 10, and 50 mg/kg, respectively. In the corresponding TNF/zVAD model,GSK2982772 shows 13, 63, and 93% protection from temperature loss over 3 h. GSK2982772 displays agood free fraction in blood in rats (4.2%), dogs (11%), cynomolgus monkeys

8、 (11%), and humans (7.4%). Theinhibitor has a good pharmacokinetic profile across both rats and monkeys. GSK2982772 distributes into arange of tissues including the colon, liver, kidney, and heart at concentrations comparable to those of blood.However, GSK2982772 has low brain penetration in rat (4%

9、) despite possessing good cell permeability(2110-6 cm/s) 1.PROTOCOLAnimal Mice: A total of 7 mice per dose group are orally predosed with saline or GSK2982772 at doses of 3, 10, andAdministration 1 50 mg/kg 15 min before i.v. administration of mouse TNF (30 g/ mouse). Temperature loss in the mice is

10、measured by a rectal probe. The study is terminated after 6 h when the control group lost 7 C 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Harris PA, et al. Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) forthe Treatment of Inflammatory Diseases. J Med Chem. 2017 Feb 23;60(4):1247-1261.McePdfHeightCaution: Product has not been full