From Serendipity to Intention: Development of Brain-Penetrant PARP1-Selective Inhibitors.

Primary and secondary brain tumors cause significant mortality and constitute an important unmet need. The development of AZD9574, a brain-penetrant, PARP1-selective inhibitor with favorable pharmacologic properties and intriguing preclinical activity, has led to an ongoing clinical trial evaluating it alone and in combination with temozolomide or antibody drug conjugates. See related article by Staniszewska et al., p. 1338.