WWZ-11-098

WWZ-11-098 is a selective CDK6 PROTAC degrader with DC₅₀ of 2.6 nM. WWZ-11-098 induces degradation of CDK6 in a CRBN-dependent manner, while sparing CDK1, CDK2, CDK4, and CDK9. WWZ-11-098 induces apoptosis, G1-S cell cycle arrest and shows anti-proliferative activity in cancer cells. WWZ-11-098 exhibits antitumor efficacy in a xenograft model without signs of toxicity. WWZ-11-098 can be used for the research of leukemia ^[1]. (Pink: CDK6 ligand; Blue: Cereblon E3 ligase ligand; Black: linker).

In Vivo, WWZ-11-098 (10 mg/kg; i.v.; daily; 21 consecutive days) drives robust, well-tolerated tumor growth inhibition in MOLT-4 xenografts mice model^[1].

In Vitro, WWZ-11-098 ( 5 days) potently inhibits the proliferation of MOLT-4 cells (IC₅₀ = 70 nM) and MV4-11 cells (IC₅₀ = 0.13 μM)^[1]. WWZ-11-098 (10 nM-10 μM; 3-24 h) potently and selectively degrades CDK6 in MOLT-4 cells with a DC₅₀ of 2.6 nM, achieving over 98% degradation at 100 nM for 24 h, while sparing CDK1, CDK2, CDK4, and CDK9, via a CRBN-dependent mechanism^[1]. WWZ-11-098 (100-200 nM; 48 h) induces G1-S cell cycle arrest and induces apoptosis in MOLT-4 cells^[1].

References:
[1]. Zhang W, et al. Discovery of WWZ-11-098: a rigid and selective CDK6 degrader. Eur J Med Chem. 2026;305:118569.