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BAY-2402234

CAS No. : 2225819-06-5

MCE 站：BAY-2402234

产品活性：BAY-2402234 是一个选择性的、二氢乳清酸脱氢酶 (DHODH) 的抑制剂，可用于骨髓恶性肿瘤 (myeloid malignancies)的相关研究。

研究领域：Metabolic Enzyme/Protease  |  Cell Cycle/DNA Damage

作用靶点：Dihydroorotate Dehydrogenase  |  DNA/RNA Synthesis

In Vitro: BAY-2402234 is a selective low-nanomolar inhibitor of human DHODH enzymatic activity. In vitro, it potently inhibits proliferation of AML cell lines in the sub-nanomolar to low-nanomolar range. BAY-2402234 induces differentiation of AML cell lines also in a sub-nanomolar to low-nanomolar range, demonstrating the anticipated mode of action in cellular mechanistic assays.

In Vivo: BAY-2402234 exhibits strong in vivo anti-tumor efficacy in monotherapy in several subcutaneous ａnd disseminated AML xenografts as well as AML patient-derived xenograft (PDX) models. Target engagement of the novel DHODH inhibitor BAY-2402234 can be observed by increase of tumoral ａnd plasma dihydroorotate levels after treatment with the inhibitor. Consistent with the in vitro data BAY-2402234 induces AML differentiation in vivo as detected by upregulation of differentiation cell surface markers in xenograft ａnd PDX models after treatment with the inhibitor. Furthermore, differentiation-associated transcriptomic changes are evident following a single administration of BAY-2402234 in vivo.

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