Nutlin-3a

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

Nutlin-3 的活性对映体可抑制 p53/MDM2 相互作用，在无细胞测定中 IC50 为 90 nM。

The active enantiomer of Nutlin-3, inhibits the p53/MDM2 interaction with IC50 of 90 nM in a cell-free assay; blocks the binding of Mdm2 to key signaling molecules such as p53 and p73α and can result in activation of cell death signaling pathways.

Nutlin-3a is a therapeutic which inhibits MDM2, activates wild-type p53, and induces apoptosis-as a therapeutic compound for TP53 wild-type ovarian carcinomas. Three cell lines (HOC-7, OVCA429 and A2780) with wild-type TP53 are highly sensitive to Nutlin-3a (IC50=4 to 6 μM). SKOV3 cells have an IC50 of 38 μM to Nutlin-3a. The two remaining ovarian clear cell lines (TOV21G and OVAS), both with TP53 wild-type, are relatively more sensitive to growth inhibition with Nutlin-3a (IC50=14 and 25 μm respectively) than the TP53 mutant cell lines. Nutlin-3a is the active enantiomer of Nutlin-3. Nutlin-3a is a highly selective MDM2 antagonist and p53 inducer. Seven days of incubation with 10 μM Nutlin-3a leads to >90% inhibition of NIH/3T3 cells’growth but does not affect the proliferation of MEF in which both targets of the drug are eliminated. Nutlin-3a effectively arrestes cell-cycle progression in all cell lines, depleting the S-phase compartment to 0.2-2% and increasing the G1- and G2/M-phase compartments, indicating G1 and G2 arrest. The p53 targets p21 and MDM2 are elevated significantly 3 h after Nutlin-3a addition and reach maximal levels at 8 h. Nutlin-3a induces apoptosis in ≈60% of SJSA-1 and MHM cells after 40 h, which increase further after 60 h (85% and 65%, respectively). T

Nutlin-3a is efficacious in all models with average tumor growth inhibition ≥98%. Nutlin-3a suppresses xenograft growth in a dose-dependent fashion with the highest dose (200 mg/kg) showing a substantial tumor shrinkage (eight partial and one full regressions). The established SJSA-1 and MHM osteosarcoma xenografts with Nutlin-3a causes extensive tumor regression.

Nutlin 3a

Apoptosis

MDM2-p53

p53/MDM2

Cancer

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675576-98-4

581.4896

C30H30Cl2N4O4

>98% (HPLC)

10 mM in DMSO

CC(C)OC1=C(C=CC(=C1)OC)C2=N[C@H]([C@H](N2C(=O)N3CCNC(=O)C3)C4=CC=C(C=C4)Cl)C5=CC=C(C=C5)Cl

2-Piperazinone, 4-[[(4S,5R)-4,5-bis(4-chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]-

(-20℃)

With Ice Pack

≥ 2 years