Evidence map›Paper›PMID 35900024›Full record

ArticleProtein science : a publication of the Protein Society2022

Structural studies of antitumor compounds that target the RING domain of MDM2.

James Ross Terrell, Sijia Tang, Oluwafoyinsola Omobodunde Faniyi, In Ho Jeong, Jun Yin, Bhavitavya Nijampatnam, Sadanandan E Velu, Wei Wang, Ruiwen Zhang, Ming Luo

RetractedOpen access · greenAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in Protein science : a publication of the Protein Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.2field-weighted citation impact, top 46% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. Structural studies of antitumor compounds that target the RING domain of MDM2.Protein science : a publication of the Protein Society · 2022
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

James Ross TerrellCenter for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA.
Sijia TangInstitute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.
Oluwafoyinsola Omobodunde FaniyiCenter for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA.
In Ho JeongDepartment of Chemistry, Georgia State University, Atlanta, Georgia, USA.
Jun YinCenter for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA.
Bhavitavya NijampatnamDepartment of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Sadanandan E VeluDepartment of Chemistry, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Wei WangDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas, USA.
Ruiwen ZhangDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas, USA.
Ming LuoCenter for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA.ORCID 0000-0003-1766-3487
Georgia State University · USDiscovery Institute · USUniversity of Alabama at Birmingham · US

Funding

Novel NFAT1-MDM2 inhibitor for Breast Cancer TherapyR01CA214019 · NCI · UNIVERSITY OF HOUSTON · PI ZHANG, RUIWEN · 2017 to 2021
$2.9M
Phase II SER-CAT Optimization: Acquisition of a next generation area detectorS10RR028976 · NCRR · UNIVERSITY OF GEORGIA · PI WANG, BI-CHENG · 2010 to 2010
$1.5M
Acquisition of a High Precision Micro Diffractometer to Support NIH funded Research at SER-CATS10OD027000 · OD · UNIVERSITY OF GEORGIA · PI ROSE, JOHN PATRICK · 2019 to 2019
$600k
NCI NIH HHS R01 CA214019NCI NIH HHS R01CA214019NCRR NIH HHS S10 RR028976NIH HHS S10 OD027000
6 · The paper itself

Abstract

Mouse double minute 2 homolog (MDM2) is an E3 ubiquitin-protein ligase that is involved in the transfer of ubiquitin to p53 and other protein substrates. The expression of MDM2 is elevated in cancer cells and inhibitors of MDM2 showed potent anticancer activities. Many inhibitors target the p53 binding domain of MDM2. However, inhibitors such as Inulanolide A and MA242 are found to bind the RING domain of MDM2 to block ubiquitin transfer. In this report, crystal structures of MDM2 RING domain in complex with Inulanolide A and MA242 were solved. These inhibitors primarily bind in a hydrophobic site centered at the sidechain of Tyr489 at the C-terminus of MDM2 RING domain. The C-terminus of MDM2 RING domain, especially residue Tyr489, is required for ubiquitin discharge induced by MDM2. The binding of these inhibitors at Tyr489 may interrupt interactions between the MDM2 RING domain and the E2-Ubiquitin complex to inhibit ubiquitin transfer, regardless of what the substrate is. Our results suggest a new mechanism of inhibition of MDM2 E3 activity for a broad spectrum of substrates.

Indexed as

Proto-Oncogene Proteins c-mdm2Tumor Suppressor Protein p53AnimalsMiceProtein BindingProtein Structure, TertiaryUbiquitinUbiquitin-Protein LigasesProto-Oncogene Proteins c-mdm2Tumor Suppressor Protein p53UbiquitinUbiquitin-Protein Ligasescrystal structuredrug designE3 ubiquitin ligaseinhibition mechanismRING finger protein

Identifiers

PMID35900024
PMCPMC9301682
OpenAlexW4286491768

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.