ADC999

ADC999 is a novel, potent, and orally available small molecule inhibitor of Wee1 kinase, developed by Almac Discovery. Wee1 is a key regulator of the G2/M cell cycle checkpoint, maintaining arrest to allow for DNA repair upon genomic stress. By inhibiting Wee1, ADC999 abrogates this checkpoint, forcing p53-deficient cancer cells with unrepaired DNA damage into premature mitosis, leading to mitotic catastrophe and apoptosis. In preclinical studies, ADC999 demonstrated single-digit nanomolar potency against Wee1, high selectivity across the kinome, and robust in vivo antitumor efficacy as a monotherapy in KRAS-mutant non-small cell lung carcinoma (NSCLC) xenograft models, as well as in combination with DNA-damaging agents.