Evidence map›Paper›PMID 39053726›Full record

ArticleCancer letters2024

An MDM2 degrader shows potent cytotoxicity to MDM2-overexpressing acute lymphoblastic leukemia cells with minimal toxicity to normal cells/tissues.

Tao Liu, Lubing Gu, Anna Mui, Zhongzhi Wu, Najah Albadari, Wei Li, Muxiang Zhou

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer letters, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

7 authors.

Tao LiuDepartment of Pediatrics and Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Lubing GuDepartment of Pediatrics and Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Anna MuiDepartment of Pediatrics and Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Zhongzhi WuDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
Najah AlbadariDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
Wei LiDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. Electronic address: wli@uthsc.edu.
Muxiang ZhouDepartment of Pediatrics and Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, GA, 30322, USA. Electronic address: mzhou@emory.edu.

Funding

Dual inhibition of MDM2 and XIAP as a therapeutic strategy in cancerR01CA240447 · NCI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI LI, WEI, ZHOU, MUXIANG · 2020 to 2024
$2.7M
Lipid nanomedicine targeting multiple signaling pathways of medulloblastomaR01NS128336 · NINDS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Ram I. Mahato · 2022 to 2026
$2.4M
Discovery of a novel MDM2-tubulin signaling pathway as a therapeutic target in AMLR01CA276135 · NCI · EMORY UNIVERSITY · PI DOUGLAS K GRAHAM, MUXIANG ZHOU · 2024 to 2026
$1.6M
NCI NIH HHS R01 CA240447NCI NIH HHS R01 CA276135NINDS NIH HHS R01 NS128336
6 · The paper itself

Abstract

The MDM2 oncogene is amplified and/or overexpressed in various human cancers and elevated expression of MDM2 protein acts as a survival factor promoting cancer progression through both p53-dependent and -independent pathways. Here, we report a novel small-molecule chemical compound (MX69-102) that we identified to induce MDM2 protein degradation, resulting in reactivation of p53, inhibition of XIAP, and potent cell growth inhibition and apoptosis in MDM2-overexpressing acute lymphoblastic leukemia (ALL) in vitro and in vivo. We have previously identified a compound (MX69) that binds to the MDM2 C-terminal RING domain and induces MDM2 protein degradation. In the present study, we performed structural modifications of MX69 and selected analog MX69-102, showing increased MDM2-targeting activity. MX69-102 exhibited significantly enhanced inhibitory and apoptotic effects on a group of MDM2-overexpressing ALL cell lines in vitro with IC

Indexed as

ApoptosisMice, SCIDPrecursor Cell Lymphoblastic Leukemia-LymphomaProto-Oncogene Proteins c-mdm2Tumor Suppressor Protein p53Xenograft Model Antitumor AssaysAnimalsAntineoplastic AgentsCell Line, TumorCell ProliferationDose-Response Relationship, DrugFemaleHumansMiceProteolysisStructure-Activity RelationshipAntineoplastic AgentsMDM2 protein, humanProto-Oncogene Proteins c-mdm2TP53 protein, humanTumor Suppressor Protein p53XIAP protein, humanX-Linked Inhibitor of Apoptosis ProteinAcute lymphoblastic leukemiaMDM2 degradationSmall-molecule inhibitor

Identifiers

PMID39053726
PMCPMC11515855

What OpenQuestion holds

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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.