WS-384 is a specific, small-molecule inhibitor dually targeting LSD1 (IC50=338.8 nM) and the DCN1-UBC12 interaction (IC50=14.8 uM).
WS-384 blocks the neddylation of cullin1 and cullin3 but had no effect on the neddylation of other cullin members in NSCLC cell, increases the levels of p21 and total level of all three isoforms of Bim (substrates of cullin 1) and NRF-2 (substrate of cullin 3).
WS-384 inhibits histone demethylation of NSCLC cells.
WS-384 inhibits cell proliferation and induced cell apoptosis in a concentration-dependent manner in A549 and H1975 cells with IC50 of 6.67 uM and 2.23 uM (24h), respectively.
WS-384 induced cell cycle arrest in A549 and H1975 cells.
WS-384 25 mg/kg and 50 mg/kg by oral administration suppresses tumor growth in A549 xenografts.
