RA-9

RA-9 is an inhibitor of deubiquitinating enzymes¹ It inhibits ubiquitin C-terminal hydrolase L1 (UCH-L1), UCH-L3, and ubiquitin-specific protease 8 (USP8) in a cell-free assay when used at a concentration of 10 µM, as well as USP5 in a reporter assay at the same concentration. RA-9 (10 µM) also inhibits the 26S proteasome, but not the 20S proteasome, in a reporter assay using HeLa cervical cancer cells. It increases the levels of polyubiquitinated proteins in HeLa and TOV-21G ovarian cancer cells when used at a concentration of 5 µM. RA-9 (10 µM) induces cell cycle arrest at the S and G₂/M phases in HeLa cells. It decreases the viability of nine cancer cell lines with IC₅₀ values ranging from 1.64 to 12.49 µM. In vivo, RA-9 (5 mg/kg every other day) increases survival and decreases tumor and ascitic fluid mass in an ES-2 ovarian cancer mouse xenograft model.²

WARNING This product is not for human or veterinary use.

1. Issaenko, O.A., and Amerik, A.Y. Chalcone-based small-molecule inhibitors attenuate malignant phenotype via targeting deubiquitinating enzymes. Cell Cycle 11(9), 1804-1817 (2012).

2. Coughlin, K., Anchoori, R., Iizuka, Y., et al. Small-molecule RA-9 inhibits proteasome-associated DUBs and ovarian cancer in vitro and in vivo via exacerbating unfolded protein responses. Clin. Cancer Res. 20(12), 3174-3186 (2014).