RA-9 是一种高选择性蛋白酶体相关的DUBs抑制剂，具有良好的毒性和抗癌活性。它阻断泛素依赖性蛋白降解而不影响 20S 蛋白酶体蛋白水解活性。它诱导卵巢癌细胞内质网应激反应，选择性诱导卵巢癌细胞株和供体原代培养细胞凋亡。

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.

Mice were inoculated i.p. with 100,000 ES-2 cells (in 100 μl DMEM) stably expressing GFP.?When tumor was detectable (approx.?6 days post inoculation), mice were randomly assigned into two groups receiving RA-9 or 0.9% saline.?Treatment with RA-9 was given i.p. on a one-day on, two-days off schedule.?The control group received the vehicle alone at the same schedule.?Working concentrations of RA-9 (10 mg/ml) were reached by dissolution in Cremophor EL and polyethylene glycol 400 (Sigma).?Prior to each injection RA-9 was further diluted in 0.9% saline (working concentration 1mg/ml).?To monitor for tumor growth, RA-9 treated and control mice were imaged with an IVIS SpectrumCT Pre-clinical in vivo imaging system (PerkinElmer) every other day.?Animals were sacrificed when abdomens became distended to twice normal size.

919091-63-7

C19H15N3O5

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DMSO:4 mg/mL (10.95 mM),ultrasonic and warming and heat to 80°C
Powder: -20°C for 3 years
In solvent: -80°C for 2 years