ETP46464

ETP46464 is a potent and selective small molecule inhibitor of the Ataxia Telangiectasia and Rad3-related (ATR) kinase. Developed by the Spanish National Cancer Research Centre (CNIO), it is widely utilized as a chemical probe to study the DNA damage response (DDR) and replication stress. By inhibiting ATR, ETP46464 prevents the phosphorylation of downstream effectors such as CHK1, thereby sensitizing cells to DNA-damaging agents or inducing synthetic lethality in cancer cells with existing DDR deficiencies. Beyond oncology, research has demonstrated its potential in fertility preservation, where it can protect the ovarian reserve from chemotherapy-induced damage (such as that caused by cyclophosphamide) by blocking apoptotic pathways in primordial follicles.