Evidence map›Paper›PMID 36431769›Full record

ArticleMolecules (Basel, Switzerland)2022

Dual Targeting of MDM4 and FTH1 by MMRi71 for Induced Protein Degradation and p53-Independent Apoptosis in Leukemia Cells.

Rati Lama, Samuel L Galster, Chao Xu, Luke W Davison, Sherry R Chemler, Xinjiang Wang

Open access · goldAbstract read
In one paragraph

Article in Molecules (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.2field-weighted citation impact, top 45% 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

3 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. Article
  3. The cross talk of ubiquitination and chemotherapy tolerance in colorectal cancer.Journal of cancer research and clinical oncology · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Rati LamaDepartment of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Samuel L GalsterDepartment of Chemistry, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
Chao XuDepartment of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Luke W DavisonDepartment of Chemistry, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
Sherry R ChemlerDepartment of Chemistry, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
Xinjiang WangDepartment of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Roswell Park Comprehensive Cancer Center · USUniversity at Buffalo, State University of New York · US

Funding

Two-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI Dean G. Tang · 1985 to 2026
$116.6M
New Methods for Nitrogen Heterocycle SynthesisR01GM078383 · NIGMS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI CHEMLER, SHERRY R · 2006 to 2023
$5.6M
Targeting Mdm2-MdmX E3 Ligase for Treatment of Drug-Resistant LymphomaR01CA208352 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI WANG, XINJIANG · 2017 to 2021
$1.9M
NCI NIH HHS R01 CA208352NIGMS NIH HHS R01 GM078383NIH HHS GM078383NIH HHS P30CA016056NIH HHS R01CA208352
6 · The paper itself

Abstract

MDM2 and MDM4 are cancer drug targets validated in multiple models for p53-based cancer therapies. The RING domains of MDM2 and non-p53-binder MDM2 splice isoforms form RING domain heterodimer polyubiquitin E3 ligases with MDM4, which regulate p53 stability in vivo and promote tumorigenesis independent of p53. Despite the importance of the MDM2 RING domain in p53 regulation and cancer development, small molecule inhibitors targeting the E3 ligase activity of MDM2-MDM4 are poorly explored. Here, we describe the synthesis and characterization of quinolinol derivatives for the identification of analogs that are capable of targeting the MDM2-MDM4 heterodimer E3 ligase and inducing apoptosis in cells. The structure-activity-relationship (SAR) study identified structural moieties critical for the inhibitory effects toward MDM2-MDM4 E3 ligase, the targeted degradation of MDM4 and FTH1 in cells, and anti-proliferation activity. Lead optimization led to the development of compound

Indexed as

LeukemiaNeoplasmsApoptosisCell Cycle ProteinsFerritinsHumansOxidoreductasesProteolysisProto-Oncogene ProteinsProto-Oncogene Proteins c-mdm2Ubiquitin-Protein LigasesCell Cycle ProteinsFerritinsFTH1 protein, humanMDM4 protein, humanOxidoreductasesProto-Oncogene ProteinsProto-Oncogene Proteins c-mdm2Ubiquitin-Protein LigasesapoptosisE3 ligaseFTH1leukemiaMDM4MMRip53quinolinolubiquitination

Identifiers

PMID36431769
PMCPMC9695299
OpenAlexW4308532065

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.