PYZD-4409 is a specific inhibitor of ubiquitin-activating enzyme UBA1 with IC50 of 20 uM.
PYZD-4409 inhibits the ATP-dependent activation of ubiquitin and subsequent transfer of the activated ubiquitin from the E1 to the common human E2 enzyme UBE2E2.
PYZD-4409 blockes the E1-dependent conjugation of ubiquitin to the E2 enzyme cdc3, induces cell death in hematologic malignant cell lines and primary patient samples preferentially over normal hematopoietic cells.
PYZD-4409 decreases tumor weight and volume without untoward toxicity in vivo.
