Ask about this productRelated genes to: MDM2 antibody
- Gene:
- MDM2 NIH gene
- Name:
- MDM2 proto-oncogene
- Previous symbol:
- -
- Synonyms:
- HDM2, MGC5370
- Chromosome:
- 12q15
- Locus Type:
- gene with protein product
- Date approved:
- 1993-12-10
- Date modifiied:
- 2017-12-01
Related products to: MDM2 antibody
Related articles to: MDM2 antibody
- Fragment-based strategies have transformed small-molecule drug discovery, yet analogous approaches for selecting noncanonical amino acids (ncAAs) in peptide drug discovery remain largely unexplored. Here we introduce an NMR-guided screening workflow that identifies individual ncAAs as "fragments" to identify privileged monomers prior to peptide library construction. Using the p53-MDM2 interaction as a benchmark system, we screened a panel of tryptophan analogs and identified 6-bromo and 6-chloro tryptophan (6Br-Trp and 6Cl-Trp) as a higher-affinity fragments relative to native Trp. Incorporation of 6Br-Trp into a model peptide improved binding to MDM2, demonstrating that amino acid affinity translates directly to peptide-level binding. We further show that 6Br-Trp and 6Cl-Trp can be efficiently charged onto tRNA and incorporated into peptides using the PURE translation system. In an mRNA display selection, peptides containing 6Br-Trp and 6Cl-Trp exhibited enhanced enrichment compared to their Trp-containing counterparts. These results show ncAA fragment screening to be a front-end strategy for guiding monomer selection in high-throughput peptide discovery via mRNA display. ncAA screening also provides a route to bias peptide libraries toward more productive chemical space to accelerate the identification of high-affinity ligands for challenging protein targets. - Source: PubMed
Castillo Abdul JJones Clark ADutra Alba CMakovsky Chelsea ALohan SandeepShakya BipasanaWalters Sara HFuglestad BrianHartman Matthew C T - To identify potential natural-product-derived inhibitors of the MDM2-p53 interaction for retinoblastoma therapy through an integrated computational screening strategy and to evaluate their binding stability, pharmacokinetic properties, and electronic characteristics. - Source: PubMed
Publication date: 2026/08/15
Geng YuleiLiu XiaoliKumar SanjayGeng Yuxin - The MDM2/p53/p14ARF axis represents a central regulatory network controlling cell-cycle progression, genomic stability, and tumor suppression, and is frequently deregulated in human cancers. In many malignancies, particularly those retaining wild-type TP53, p53 activity is functionally suppressed through MDM2 overexpression or CDKN2A (p14ARF) loss, events that may be reversed in order to activate this pathway. This review explores the biological basis of the MDM2/p53/p14ARF axis and its relevance as a target for gene therapy and multimodal treatment strategies. While gene therapy for the restoration of p53 has been extensively explored, the use of genetic interventions for the inhibition of MDM2 or the restoration of p14ARF is underrepresented, though they have the potential to re-establish DNA damage responses, promote apoptosis, and enhance tumor sensitivity to chemotherapy and radiotherapy. In addition, p53 activation is now recognized as a contributor to immunogenic cell death and modulation of the tumor microenvironment. Laboratory and early clinical studies demonstrate that inhibition of MDM2 and restoration of p14ARF by gene transfer can integrate tumor cytotoxicity with immune activation. Although large-scale clinical validation remains limited, current evidence supports the MDM2/p53/p14ARF axis as a promising, context-dependent target within biomarker-driven combination therapies rather than a standalone approach. - Source: PubMed
Publication date: 2026/09/21
de Oliveira Soraia BarbosaAlves Ana Laura VieiraNiitsuma Bianca NaomiAntunes FernandaMarinho Gabriel BorelAmanatidis Giovanna LagonegroLuz JeanBarbosa MarianaZambotti Pedro Egydio OliveiraRodrigues Otavio AugustoStrauss Bryan E - Primary cardiac malignancies are rare and often present with non-specific clinical and imaging findings, leading to diagnostic delays. We report a case of a 76-year-old woman with progressive dyspnea who was found to have a left atrial mass initially suspected to be a thrombus or benign lesion because of the absence of significant uptake on fluorodeoxyglucose positron emission tomography (FDG-PET). However, progressive enlargement and infiltrative imaging features raised concern for malignancy. Histopathological evaluation ultimately confirmed undifferentiated pleomorphic sarcoma with MDM2 amplification, consistent with intimal sarcoma. This case highlights the limitations of FDG-PET in excluding cardiac malignancy and underscores the importance of integrating multimodal imaging with clinical suspicion to avoid diagnostic anchoring. - Source: PubMed
Publication date: 2026/08/20
Sweidan Hisham BZhu Feng - Rezatapopt (PC14586), a first-in-class Y220C-selective p53 reactivator, demonstrates single-agent clinical efficacy; however, combinatorial strategies may enhance clinical outcomes. Here, we evaluated rezatapopt in combination with standard-of-care agents (chemotherapy and bevacizumab), murine double minute 2 (MDM2) inhibitors, and a library of FDA-approved compounds. While chemotherapy, bevacizumab, and MDM2 inhibitors showed in vivo efficacy, a high-throughput screen identified the phosphoinositide 3-kinase (PI3K)/ Protein Kinase B (AKT)/mechanistic target of rapamycin (mTOR) and mitogen-activated protein kinase pathways as top synergistic candidates. Validation confirmed that PI3Kα inhibition synergized with rezatapopt to deepen apoptosis and tumor growth inhibition in xenograft models. Thus, PI3K/mTOR pathway inhibition may represent a clinically actionable, conserved p53-reactivation vulnerability across diverse histologies harboring a TP53 Y220C mutation. - Source: PubMed
Publication date: 2026/09/18
Ahmed TamerMichaud Erin EXu LizhongYang HongLi WenhuiLu LingMcBrayer Mary KateSun YvonneRusso Brandon MMulligan Chris LBattaglia JoshDumble Melissa LLevine Arnold JPuzio-Kuter Anna MPoyurovsky Masha V