RA-9

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

RA-9 是一种有效的、选择性的蛋白酶体相关去泛素化酶 (DUB) 抑制剂，具有良好的毒性和抗癌活性。

RA-9 is a potent and selective proteasome-associated inhibitor of deubiquitinating enzymes (DUBs), with favorable toxicity profile and anticancer activity. RA-9 selectively induces apoptosis in ovarian cancer cell lines.The characterization of RA-9 as a small-molecule inhibitor of proteasome-associated DUBs.?Treatment with RA-9 selectively induces onset of apoptosis in ovarian cancer cell lines and primary cultures derived from donors.?Loss of cell viability following RA-9 exposure is associated with an unfolded protein response as mechanism to compensate for unsustainable levels of proteotoxic stress.?In vivo treatment with RA-9 retards tumor growth, increases overall survival, and was well tolerated by the host.

Cell Viability Assay Cell Line:Cisplatin-sensitive ovarian cancer cell lines TOV-21G and ES-2, Cisplatin-resistant ovarian cancer cell lines HEY and OVCAR-3, primary ovarian cancer cellsConcentration:10, 20, 30 μM Incubation Time:48 hours Result:Compromised the viability of ovarian cancer cells in a dose-dependent fashion.Cell Cycle Analysis Cell Line:ES-2 cells Concentration:1.25, 5 μM Incubation Time:18 hours Result:Resulted in a dose-dependent increase in the fraction of ES-2 cells in the G2-M cell cycle phase.Western Blot Analysis Cell Line:ES-2, SKOV-3 and TOV-21G ovarian cancer cells Concentration:5 μM Incubation Time:0-24 h Result:Caused a time-dependent increase in the steady levels of the early ER-stress marker GRP-78, as well as the late ER-stress markers IRE1-α and Ero1L-α.

Animal Model:Six-week-old female immunodeficient (NCr nu/nu) mice Dosage:5 mg/kg Administration:I.p; one-day on, two-days off Result:Significant reduction in tumor burden at day 12.

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Apoptosis

Apoptosis

Apoptosis|deubiquitinating enzymes (DUBs)

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919091-63-7

365.34

C19H15N3O5

>98% (HPLC)

DMSO:4 mg/mL (10.95 mM; ultrasonic and warming and heat to 80°C)

[O-][N+](=O)c1ccc(\C=C2/CNC\C(=C/c3ccc(cc3)[N+]([O-])=O)C2=O)cc1

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(-20℃)

With Ice Pack

≥ 2 years