AZD-9574(CAS No.:2756333-39-6) is a potent and brain penetrant PARP1 inhibitor

AZD-9574 is a potent, blood-brain barrier (BBB) penetrant and PARP1 selective inhibitor. AZD9574 can be used for primary and secondary brain malignancies research. AstraZeneca evaluated the efficacy of AZD9574 with an intracranial xenotransplantation model of breast cancer brain metastasis. The preliminary results showed that 3 mg/kg AZ9574 showed significant tumor growth inhibition on the animal model of intracranial lesions, significantly prolonged the survival period of tumor bearing mice, and was expected to provide a new treatment scheme for patients with HRD+breast cancer brain metastasis.The first generation PARP inhibitor cannot enter the brain, so it cannot treat patients with brain metastases. The developed AZD9574 has more than 8000 times the selectivity to PARP1 than other subtypes, and is more effective in entering the brain, giving play to the efficacy, further reducing the therapeutic dose, and improving the Therapeutic index.

AZD-9574 is a potent and brain penetrant PARP1 inhibitor and shows >8000-fold selectivity for PARP1 compared to PARP2/3/5a/6. AZD-9574 acts by selectively inhibiting and trapping PARP1 at the sites of SSBs. AZD-9574 is an anti-cancer agent and can be used for HRD+ breast cancer and advanced solid malignancies research.