BAY-2402234 is an inhibitor of dihydroorotate dehydrogenase (DHODH) for the treatment of myeloid malignancies.BAY 2402234 is a selective low-nanomolar inhibitor of human DHODH enzymatic activity.

BAY-2402234 induces differentiation of AML cell lines also in a sub-nanomolar to low-nanomolar range which demonstrates the anticipated mode of action in cellular mechanistic assays[1]. BAY-2402234 is a selective low-nanomolar inhibitor of human DHODH enzymatic activity. It potently inhibits proliferation of AML cell lines in the sub-nanomolar to low-nanomolar range in vitro.

BAY-2402234 demonstrates potent in vivo anti-tumor effectiveness as a single agent across various AML (acute myeloid leukemia) xenograft models, including subcutaneous, disseminated, and patient-derived (PDX) forms. It promotes AML cell differentiation, evident through increased differentiation cell surface markers in treated xenograft and PDX models. The engagement of this novel DHODH (dihydroorotate dehydrogenase) inhibitor is confirmed by elevated dihydroorotate levels in tumor tissues and plasma post-treatment. Additionally, transcriptomic analyses reveal differentiation-related changes after a single dose of BAY-2402234, underscoring its mechanistic impact on AML cells[1].