molecules of the month

Context. AZD1390 (recently published on by University of Minnesota) is a brain-penetrating Ataxia-Telangiectasia Mutated (ATM) kinase inhibitor under development for brain tumors. The kinase, known for its critical role in the repair of lethal DNA lesions induced by radiotherapy treatment, is considered an attractive target for CNS tumors because coupling its inhibition with radiotherapy may lead to radiosensitization of tumor cells. In a recent publication, University of Minnesota scientists investigated the CNS penetration of AZD1390 in mice using transporter knockout models lacking efflux transporters P-gp and Bcrp. Although the compound was found to be an active substrate of P-gp which limited its CNS exposure, effective total concentrations for radiosensitization were still achieved. The compound is currently being evaluated in four…