(±)-Nutlin-3

(±)-Nutlin-3 is a small-imidazoline-based mouse double minute 2 (MDM2) protein antagonist which disrupts MDM2-p53 interaction (IC₅₀ = 0.09 μM; Vassilev et al.). MDM2 binds the p53 tumor suppressor protein with high affinity and negatively modulates its transcriptional activity and stability. By disrupting this interaction, (±)-Nutlin-3 therefore promotes the expression of p53-regulated genes and exhibits potent antiproliferative activity in cells with functional p53, but not in cells with mutated p53 (Vassilev et al., Gu et al.).

CANCER RESEARCH

• Inhibits the proliferation of exponentially growing human skin fibroblasts (IC₅₀ = 2.2 μM) and mouse embryonic fibroblasts (IC₅₀ = 1.3 μM), and suppresses the growth of established tumor xenografts in mice (Vassilev et al.).
• Leads to G1 cell-cycle arrest in HCT116 colon carcinoma cell line expressing wild-type p53 and p21 (Benson et al.).
• Induces p53-mediated apoptosis in solid tumor and pediatric acute lymphoblastic leukemia cell lines (Gu et al.; Vaseva et al.)