ArticleThe Journal of biological chemistry2010
Identification and characterization of the first small molecule inhibitor of MDMX.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
105 citing papers in PubMed, 193 citations in OpenAlex.
- Development of MDM2-Targeting PROTAC for Advancing Bone Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Targeting Hdm2 and Hdm4 in Anticancer Drug Discovery: Implications for Checkpoint Inhibitor Immunotherapy.Cells · 2024Review
- Computational approaches for the design of modulators targeting protein-protein interactions.Expert opinion on drug discovery · 2023Review
- Review
- Pharmacological inhibition of MDM4 alleviates pulmonary fibrosis.Theranostics · 2023Article
- MDMX elevation by a novel Mdmx-p53 interaction inhibitor mitigates neuronal damage after ischemic stroke.Scientific reports · 2022Article
- Review
- Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX.Molecules (Basel, Switzerland) · 2022Article
- Advanced Strategies for Therapeutic Targeting of Wild-Type and Mutant p53 in Cancer.Biomolecules · 2022Review
- Leveraging the multivalent p53 peptide-MdmX interaction to guide the improvement of small molecule inhibitors.Nature communications · 2022Article
- It's Getting Complicated-A Fresh Look at p53-MDM2-ARF Triangle in Tumorigenesis and Cancer Therapy.Frontiers in cell and developmental biology · 2022Review
- Tumor suppressor p53: Biology, signaling pathways, and therapeutic targeting.Biochimica et biophysica acta. Reviews on cancer · 2021Review
- Identification of Secondary Binding Sites on Protein Surfaces for Rational Elaboration of Synthetic Protein Mimics.ACS chemical biology · 2021Article
- Computational Modeling as a Tool to Investigate PPI: From Drug Design to Tissue Engineering.Frontiers in molecular biosciences · 2021Review
- Retinoblastoma: Etiology, Modeling, and Treatment.Cancers · 2020Review
- Identification of a Structural Determinant for Selective Targeting of HDMX.Structure (London, England : 1993) · 2020Article
- Small-molecule MDM2/X inhibitors and PROTAC degraders for cancer therapy: advances and perspectives.Acta pharmaceutica Sinica. B · 2020Review
- Focused Library Generator: case of Mdmx inhibitors.Journal of computer-aided molecular design · 2020Article
- Recent Synthetic Approaches towards Small Molecule Reactivators of p53.Biomolecules · 2020Review
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
The p53 pathway is disrupted in virtually every human tumor. In approximately 50% of human cancers, the p53 gene is mutated, and in the remaining cancers, the pathway is dysregulated by genetic lesions in other genes that modulate the p53 pathway. One common mechanism for inactivation of the p53 pathway in tumors that express wild-type p53 is increased expression of MDM2 or MDMX. MDM2 and MDMX bind p53 and inhibit its function by distinct nonredundant mechanisms. Small molecule inhibitors and small peptides have been developed that bind MDM2 in the p53-binding pocket and displace the p53 protein, leading to p53-mediated cell cycle exit and apoptosis. To date, peptide inhibitors of MDMX have been developed, but no small molecule inhibitors have been reported. We have developed biochemical and cell-based assays for high throughput screening of chemical libraries to identify MDMX inhibitors and identified the first MDMX inhibitor SJ-172550. This compound binds reversibly to MDMX and effectively kills retinoblastoma cells in which the expression of MDMX is amplified. The effect of SJ-172550 is additive when combined with an MDM2 inhibitor. Results from a series of biochemical and structural modeling studies suggest that SJ-172550 binds the p53-binding pocket of MDMX, thereby displacing p53. This lead compound is a useful chemical scaffold for further optimization of MDMX inhibitors that may eventually be used to treat pediatric cancers and various adult tumors that overexpress MDMX or have similar genetic lesions. When combined with selective MDM2 inhibitors, SJ-172550 may also be useful for treating tumors that express wild-type p53.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.