WS-383 is a potent, selective and reversible inhibitor of DCN1-UBC12 interaction, with an IC 50 of 11 nM. WS-383 inhibits Cul3/1 neddylation, induces accumulation of p21, p27 and NRF2
In Vitro
WS-383 (10 μM) is against a panel of kinases such as BTK, CDKs, and EGFR [L858R] using staurosporine and BIBW 2992 as the positive controls. WS-383 showed weak inhibitory activity at 10.0 μM,it is selective to the DCN1-UBC12 interaction over the selected kinasesr. WS-383 (0.03-3 μM;24 hours) blocks Cul3 neddylation at 3 μM and also has certain inhibition of Cul1 neddylation at 10 μM but was not effective in inhibiting neddylation of other cullin members. WS-383 (0.03-3 μM;24 hours) increases Cul1, Skp1 (adaptor protein), F-box protein, and RBX1/RBX2 RING protein form SCF E3 complex. Cyclin dependent kinase inhibitor 1A (p21) and cyclin dependent kinase inhibitor 1B (p27) expression in a dose-dependent manner in MGC-803 and KYSE70 manner. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: MGC-803 cells Concentration: 0.03 μM; 0.3 μM; 3 μM; 10 μM Incubation Time: 24 hours Result: Decreased N8-Cul1 and N8-Cul2 protein expression. Western Blot AnalysisCell Line: MGC-803 and KYSE70 cells Concentration: 0.03 μM; 0.3 μM; 3 μM; 10 μM Incubation Time: 24 hours Result: Induced accumulation of p21, p27, and NRF2 in MGC-803 cells.
