Nutlin-3

Research use only, not for human use.

Nutlin-3 is MDM2 antagonist. Nutlin-3 inhibits the MDM2-p53 interaction (IC50 = 0.09 μM) and activates p53.

Nutlin-3 is MDM2 antagonist. Nutlin-3 inhibits the MDM2-p53 interaction (IC50 = 0.09 μM) and activates p53. Antiproliferative agent;chemotherapeutic agent; induces apoptosis in Y cells.

Nutlin-3 is an inhibitor of the MDM2-p53 interaction. In particular, co-treatment of p53-positive HCT116 cells with 1 μM of Inauhzin and 2 μM of Nutlin-3 more significantly activated p53 as measured by its protein level as well as the level of its target p21, PUMA or cleaved PARP as indication of apoptosis. Nutlin-3 is a small-molecule inhibitor that acts to inhibit MDM2 binding to p53 and subsequent p53-dependent DNA damage signaling. As a single agent, Nutlin-3 (2-10 μM) stabilizes p53 and p21WAF levels and is toxic to WTp53-22RV1 cells (IC50, 4.3 μM) but has minimal toxicity toward p53-deficient cells (IC50, >10 μM). Nutlin-3 induces p53 and p21WAF expression in a dose-dependent manner in 22RV1 cells. Short-term cell cycle assays show that, at a dose of 10 μM, Nutlin-3 increasea slightly the G1-phase fraction and decreasea S-phase fraction of all three cell lines.

Nutlin-3 can suppress the growth of xenograft tumors derived from human osteosarcoma or leukemia cells, the anti-tumor activity of Nutlin-3 even at the dose of 200 mg/kg per oral administration is marginal in an HCT116-derived xenograft tumor model. Nutlin-3 may be a useful adjunct to improve the therapeutic ratio using precision radiotherapy targeted to hypoxic cells and warrants further study in vivo.

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Apoptosis

MDM2-p53

p53-MDM2

Cancer

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548472-68-0

581.49

C30H30Cl2N4O4

>98% (HPLC)

DMSO: 10 mM

COC1=CC(OC(C)C)=C(C=C1)C1=NC(C(N1C(=O)N1CCNC(=O)C1)C1=CC=C(Cl)C=C1)C1=CC=C(Cl)C=C1

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(-20℃)

With Ice Pack

≥ 2 years