WK369 (WK-369) is a specific small molecule inhibitor of BCL6, directly binds to the BCL6-BTB domain (SPR KD=2.24 uM) and blocks the interaction between BCL6 and SMRT with IC50 of 0.32 uM in HTRF assays.
WK369 exhibits excellent binding affinities to BCL6-BTB domain with IC50 of <2 uM in HTRF assays, 120 times higher potent than that of FX1 (Cat# PC-60927).
WK369 inhibits the transcriptional repressor activity of BCL6-BTB in a dose dependent manner in vitro and in vivo, but without any effect on the other BTB zinc finger repressors (Kaiso and PLZF).
WK369 significantly reactivates multiple BCL6-target genes including ATR, CD69, p53 and CDKN1A.
WK369 inhibits ovarian cancer cell growth, migration and induces apoptosis.
WK369 prevents ovarian cancer growth, suppresses ovarian cancer intra-abdominal metastasis in vivo.
WK369 sensitizes ovarian cancer to chemotherapy on SKOV3 xenograft mouse models, inhibits AKT and MEK/ERK signaling pathway by targeting BCL6.