nutlin-3

Overview

Nutlin-3 is a cis-imidazoline MDM2 antagonist that stabilizes wild-type p53 by blocking the p53-MDM2 interaction. It is the racemic parent compound; nutlin-3a is the active enantiomer. Both nutlin-3 and the more potent clinical-stage analogue AMG-232 are nominated as therapeutic strategies in tumors with MDM2 focal amplification. In TCGA melanoma, MDM2 amplifications are enriched in the Triple-WT subtype.

Evidence in the corpus

• MDM2 focal amplifications enriched in Triple-WT melanoma subtype (14% of 318 TCGA cases; no hot-spot BRAF/RAS/NF1); nutlin-3 and AMG-232 nominated as MDM2-inhibitor strategies for MDM2-amplified, BCL2-high tumors in this subgroup PMID:26091043
• MDM2 inhibitor; showed antiproliferative and apoptotic synergy with cisplatin in TP53 wild-type, cisplatin-resistant GCT cell lines in vitro; MDM2 amplification present in 7.6% of cisplatin-resistant GCT PMID:27646943

Resistance mechanisms

Cancer types (linked)

• MEL

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:27646943

This page was processed by wiki-cli on 2026-05-14.