APR-1051

APR-1051 is a next-generation, highly selective, oral small molecule inhibitor of WEE1 kinase, developed by Aprea Therapeutics for the treatment of advanced solid tumors with specific cancer-associated gene alterations. WEE1 kinase is a serine/threonine-protein kinase involved in cell cycle regulation and DNA damage response; its inhibition can induce synthetic lethality in tumor cells with defective p53 or other DNA repair pathways. APR-1051 has been designed to minimize off-target toxicity—particularly avoiding inhibition of the polo-like kinase (PLK) family—and to provide improved pharmacokinetic properties and safety compared to earlier WEE1 inhibitors. Preclinical studies have shown potent anti-proliferative activity (IC₅₀ values 8.9–230 nM), activation of cGAS/STING-mediated immunogenic cell death, and synergy with anti–PD-1 therapies in HPV-positive head and neck squamous cell carcinoma models. Early clinical data from ongoing Phase 1 trials indicate that APR-1051 is safe and well-tolerated at subtherapeutic doses, with no dose-limiting toxicities or significant hematologic adverse events observed[1][5][6][8].

Other names

APR-1051APR1051APR 1051