MLN-4924

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

5'-单磷酸腺苷的类似物，有效且选择性地抑制 NEDD8 激活酶 (NAE)，IC50 为 4.7 nM。

An analog of adenosine 5’-monophosphate that potently and selectively inhibits NEDD8-activating enzyme (NAE) with IC50 of 4.7 nM; also inhibits the related enzymes ubiquitin-activating enzyme (UAE) and SUMO-activating enzyme (SAE) with IC50 of 1.5 and 8.2 uM, respectively; disrupts CRL-mediated protein turnover leading to apoptosis in HCT116 cells, suppresses the growth of human tumor xenografts in mice (30-60 mg/kg).Blood Cancer Phase 2 Clinical(In Vitro):Pevonedistat (MLN4924) is a potent inhibitor of NAE, and is selective relative to the closely related enzymes UAE, SAE, UBA6 and ATG7 (IC50=1.5, 8.2, 1.8 and >10 μM, respectively) when evaluated in purified enzyme assays that monitor the formation of E2-UBL thioester reaction products. Pevonedistat (MLN4924) selectively inhibits NAE activity compared to the closely related ubiquitin-activating enzyme (UAE, also known as UBA1) and SUMO-activating enzyme (SAE; a heterodimer of SAE1 and UBA2 subunits), in purified enzyme and cellular assays. MLN4924 exhibits potent cytotoxic activity against a variety of human tumour-derived cell lines.(In Vivo):Pevonedistat (MLN4924) (sc, 10 mg/kg, 30 mg/kg, or 60 mg/kg) inhibits the NEDD8 pathway resulting in DNA damage in Mice bearing HCT-116 xenografts.Pevonedistat (sc, 120 mg/kg) and TNF-α (10 μg/kg) synergistically cause liver damage in SD rats.

Pevonedistat (MLN4924) is a potent inhibitor of NAE, and is selective relative to the closely related enzymes UAE, SAE, UBA6 and ATG7 (IC50=1.5, 8.2, 1.8 and >10 μM, respectively) when evaluated in purified enzyme assays that monitor the formation of E2-UBL thioester reaction products. Pevonedistat (MLN4924) selectively inhibits NAE activity compared to the closely related ubiquitin-activating enzyme (UAE, also known as UBA1) and SUMO-activating enzyme (SAE; a heterodimer of SAE1 and UBA2 subunits), in purified enzyme and cellular assays. MLN4924 exhibits potent cytotoxic activity against a variety of human tumour-derived cell lines.

Pevonedistat (MLN4924) (sc, 10 mg/kg, 30 mg/kg, or 60 mg/kg) inhibits the NEDD8 pathway resulting in DNA damage in Mice bearing HCT-116 xenografts.Pevonedistat (sc, 120 mg/kg) and TNF-α (10 μg/kg) synergistically cause liver damage in SD rats.

Pevonedistat | TAK-924

Proteasome/Ubiquitin

NEDD8

NAE

Cancer

Blood cancer

905579-51-3

443.5193

C21H25N5O4S

>98% (HPLC)

DMSO: ≥ 111.25 mg/mL

C1CC2=CC=CC=C2[C@H]1NC3=NC=NC4=C3C=CN4[C@@H]5C[C@H]([C@H](C5)O)COS(=O)(=O)N

Sulfamic acid, [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl ester

(-20℃)

With Ice Pack

≥ 2 years