Discovery of Highly Potent and Orally Available CCNK Molecular Glue Degraders as Broad-Spectrum Antitumor Agents

= 6.82 h). Moreover, ZLY025 induced the highly selective degradation of CCNK with low off-target degradation effects in TMT-based global proteomic analysis. In the xenografted model, ZLY025 exerted robust antitumor activity by effectively degrading CCNK. In the subacute toxicity study, ZLY025 exhibited adequate safety profiles even at the sustaining high dose of 200 mg/kg. Based on these positive results, ZLY025 is worthy of further evaluation as the first highly potent and orally available CCNK molecular glue degrader.