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PYZD-4409 is a novel potent, selective and cell permeable inhibitor of ubiquitin-activating enzyme (E1). It induces cell death in hematologic malignant cell lines and primary patient samples preferentially over normal hematopoietic cells. PYZD-4409 blocks degradation of the short-lived proteins p53 and cyclin D3. It inhibits NF-κB activation and induces cell death associated with ER stress. It also displays antitumor effects in a mouse model of leukemia by intraperitoneal administration of the drug. 

How to Use:

• In vitro:  PYZD-4409 was used at 10-30 µM final concentration in various in vitro assays. 
• In vivo: PYZD-4409 was dosed intraperitoneally to the mouse model of leukemia (MDAY-D2 murine leukemia cells) at 10 mg/kg once per day. 

Reference:

1. 1.Xu GW, et al. The ubiquitin-activating enzyme E1 as a therapeutic target for the treatment of leukemia and multiple myeloma. (2010) Blood. 115(11):2251-9.