GSK2982772 - RIPK1 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGSK2982772Cat. No.: HY-101760CAS No.: 1622848-92-3分式: CHNO分量: 377.4作靶點(diǎn): RIP kinase作通路: Apoptosis儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 100 mg/mL (264.97 mM)* means soluble, but sat

2、uration unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液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請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前?qǐng)先配制澄清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根

3、據(jù)儲(chǔ)存條件，適當(dāng)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(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.62 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.62 mM); Clear solution3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oil1/2 Master of Small Molecule

4、s 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (6.62 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 GSK2982772可服的、有效的ATP競(jìng)爭(zhēng)型的RIP1酶抑制劑，對(duì)和猴 RIP1 的IC50值分別為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體外研究 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.體內(nèi)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