RA190 _Proteasome 抑制剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERA190Cat. No.: HY-100739CAS No.: 1617495-03-0分式: CHClNO分量: 596.76作靶点: Proteasome作通路: Metabolic Enzyme/Protease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 (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 您边的抑制剂师www.MedChemE物活性 RA190双亚苄 哌啶，通过与泛素受体RPN13的半胱氨酸88共价结合来抑制蛋酶体功能。IC50 & Target IC50: 0.15 M (HeLa cell)体外研究 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.体内研究 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.