WK499 (WK-499) is a small molecule inhibitor of BCL6 with IC50 of 11.7 nM in HTRF assay, directly binds to BCL6 BTB (SPR KD=148 nM), inhibits the BCL6-mediated transcriptional repression activity.
WK499 is >3,000-fold more potent than the previously reported BCL6 inhibitor FX1 (IC50 = 37.68 µM, Cat#PC-60927) and comparable to that of the depressant BI3802 (IC50 = 2.7 nM, Cat#PC-60949).
WK499 inhibits the transcriptional activity of BCL6BTB in a concentration dependent manner in luciferase reporter assay, and the transcriptional activity is almost destroyed at 2.5 µM, whereas FX1 and BI3802 has little effect on the BCL6BTB even at 20 uM.
WK499 inhibits the proliferation of glioma cells with high expression of BCL6 in vitro.
WK499 reactivates BCL6 downstream genes and induces apoptosis of GBM cells, induces the degradation of BCL6 and inhibits its function of promoting cancer.
WK499 (12.5 mg/kg, i.p.) inhibits tumor growth in the preclinical GBM xenografts, effectively enhance the therapeutic effect of TMZ on GBM.