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Description: AZ32 is a novel, potent and orally bioavailable and blood-brain barrier-penetreable ATM inhibitor (AZ32) that radiosensitizes intracranial gliomas in mice. AZ32 was highly efficient in vivo as radiosensitizer in syngeneic and human, orthotopic mouse glioma model compared with AZ31. AZ32 is the first ATMi with oral bioavailability shown to radiosensitize glioma and improve survival in orthotopic mouse models. These findings support the development of a clinical-grade, BBB-penetrating ATMi for the treatment of GBM. Importantly, because many GBMs have defective p53 signaling, the use of an ATMi concurrent with standard radiotherapy is expected to be cancer-specific, increase the therapeutic ratio, and maintain full therapeutic effect at lower radiation doses.
References: Mol Cancer Ther. 2018 Aug; 17(8):1637-1647.
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