Evidence map›Paper›PMID 41986621›Full record

ArticleLeukemia2026

Activity of PROTAC MDM2 degrader in primary leukemia cells and PDX models.

Malathi Kandarpa, Luke F Peterson, Harish Potu, Megha Ramappan, Yihong Liu, Avery Polk, Shaomeng Wang, Moshe Talpaz

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Leukemia, 2026. 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. Article
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

8 authors.

Malathi KandarpaDepartment of Internal Medicine, Division of Hematology & Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
Luke F PetersonDepartment of Internal Medicine, Division of Hematology & Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
Harish PotuDepartment of Internal Medicine, Division of Hematology & Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
Megha RamappanDepartment of Internal Medicine, Division of Hematology & Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
Yihong LiuDepartment of Internal Medicine, Division of Hematology & Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
Avery PolkDepartment of Internal Medicine, Division of Hematology & Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
Shaomeng WangDepartment of Internal Medicine, Division of Hematology & Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-8782-6950
Moshe TalpazDepartment of Internal Medicine, Division of Hematology & Oncology, University of Michigan Medical School, Ann Arbor, MI, USA. mtalpaz@umich.edu.ORCID http://orcid.org/0000-0003-3361-3981

Funding

Small-molecule MDM2 degradersR01CA219345 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WANG, SHAOMENG · 2017 to 2021
$3.1M
U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA219345
6 · The paper itself

Abstract

MDM2 is an E3 ubiquitin ligase that promotes p53 tumor suppressor degradation and has emerged as a therapeutic target in the treatment of wild-type (wt) TP53 tumors. In acute myeloid leukemia (AML), TP53 mutations are infrequent (15-20%), but wt-p53 is often inactivated through overexpression of MDM2. Thus, MDM2 inhibitors are currently in clinical trials for AML. However, p53 stabilization with inhibitors upregulates MDM2, which limits their clinical efficacy. Proteolysis-targeting chimeric (PROTAC) molecules that degrade MDM2 may overcome this feedback. MD-265 is a PROTAC that recruits CRBN, degrades MDM2, restores p53 and induces apoptosis. We tested MD-265 in ex vivo cultures of 105 primary leukemic stem cells (LSCs). The median cytotoxic IC

Indexed as

Leukemia, Myeloid, AcuteProto-Oncogene Proteins c-mdm2AnimalsApoptosisHumansMiceNeoplastic Stem CellsProteolysisProteolysis Targeting ChimeraTumor Suppressor Protein p53Xenograft Model Antitumor AssaysMDM2 protein, humanProteolysis Targeting ChimeraProto-Oncogene Proteins c-mdm2Tumor Suppressor Protein p53

Identifiers

PMID41986621
PMCPMC13149300

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.