ATRIN-333

ATRIN-333 is a next-generation macrocyclic small molecule inhibitor of the Ataxia telangiectasia and Rad3-related (ATR) protein kinase. Developed by ATRIN Pharmaceuticals in collaboration with researchers at Yale University, it targets the DNA damage response (DDR) pathway, specifically inhibiting the repair of replication-induced DNA damage. In preclinical studies for glioblastoma (GBM), ATRIN-333 has been encapsulated in poly(ethylene glycol)-co-poly(ethylene brassylate-co-dioxanone) (PEG-EB-co-DO) nanoparticles and delivered via convection-enhanced delivery (CED). This localized delivery method bypasses the blood-brain barrier and has demonstrated potent synergy with systemic alkylating agents like lomustine, significantly extending survival in intracranial tumor models without inducing systemic hematological toxicity.