RA190 _Proteasome 抑制劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERA190Cat. No.: HY-100739CAS No.: 1617495-03-0分式: CHClNO分量: 596.76作靶點: Proteasome作通路: Metabolic Enzyme/Protease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 (167.57 mM)H2O : 40%

2、PEG300 5% Tween-80 45% salineSolubility: 2.38 mg/mL (3.99 mM); Clear solutionBIOLOGICAL ACTIVITY1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemE物活性 RA190雙亞芐 哌啶，通過與泛素受體RPN13的半胱氨酸88共價結合來抑制蛋酶體功能。IC50 & Target IC50: 0.15 M (HeLa cell)體外研究 RA190 covalently binds to cysteine 88 of ubiquitin receptor RPN1

3、3 in the 19S regulatory particle and inhibitsproteasome function, triggering rapid accumulation of polyubiquitinated proteins. Multiple myeloma (MM)lines, even those resistant to bortezomib, are sensitive to RA190 via endoplasmic reticulum stress-relatedapoptosis. RA190 stabilizes targets of human p

4、apillomavirus (HPV) E6 oncoprotein, and preferentially killsHPV-transformed cells 1.體內研究 RA190 distributes to plasma and major organs excepting brain, and inhibits proteasome function in skin andmuscle. RA190 administration profoundly reduces growth of multiple myeloma and ovarian cancerxenografts,

5、and oral RA190 treatment retards HPV16+ syngeneic mouse tumor growth, without impactingspontaneous HPV-specific CD8+ T cell responses 1.PROTOCOLCell Assay 1 RA190 is dissolved in DMSO and diluted with cell culture medium. HeLa cells are treated with RA190 (0.2,0.4, 0.6, 0.8, 1, 2, 3, 4, 5 M) for 48

6、hr. Cell viability is assayed using commerical kit 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: Mice are divided into two groups and treated daily i.p. with RA190 (10 mg/kg) or vehicle, and imagedAdministration 1 again on day 7 and day

7、 14. NOG mice (5 per group) are inoculated with 1X106 NCI-H929-GFP-Luc cells i.v.,and after 4 weeks, mice are imaged for their luciferase activity and divided into two groups. Mice are treatedi.p. with RA190 (20 mg/kg) or vehicle, and imaged again at the end of the treatment for their luciferaseacti

8、vity 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Anchoori RK, et al. A bis-benzylidine piperidone targeting proteasome ubiquitin receptor RPN13/ADRM1 as a therapy for cancer. CancerCell. 2013 Dec 9;24(6):791-805.McePdfHeightCaution: Product has not been fully validated for medical applications.