Evidence map›Paper›PMID 34289376›Full record

ArticleCell chemical biology2021

Development of potent dimeric inhibitors of GAS41 YEATS domain.

Dymytrii Listunov, Brian M Linhares, EunGi Kim, Alyssa Winkler, Miranda L Simes, Sidney Weaver, Hyo Je Cho, Alexandrea Rizo, Sergey Zolov, Venkateshwar G Keshamouni and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.7field-weighted citation impact, top 13% 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

16 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Histone crotonylation in tumors (Review).Molecular and clinical oncology · 2025
    Review
  6. Review
  7. Article
  8. Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024
    Review
  9. Article
  10. Crotonylation modification and its role in diseases.Frontiers in molecular biosciences · 2024
    Review
  11. Small-molecule tools for YEATS domain proteins.Current opinion in chemical biology · 2023
    Review
  12. Review
  13. Review
  14. Histone Readers and Their Roles in Cancer.Cancer treatment and research · 2023
    Article
  15. Review
  16. 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

12 authors at 1 institution in 1 country.

Dymytrii ListunovDepartment of Pathology, University of Michigan, 1150 West Medical Center Dr, MSRB I, Room 4510D, Ann Arbor, MI 48108, USA.
Brian M LinharesDepartment of Pathology, University of Michigan, 1150 West Medical Center Dr, MSRB I, Room 4510D, Ann Arbor, MI 48108, USA.
EunGi KimDepartment of Pathology, University of Michigan, 1150 West Medical Center Dr, MSRB I, Room 4510D, Ann Arbor, MI 48108, USA.
Alyssa WinklerDepartment of Pathology, University of Michigan, 1150 West Medical Center Dr, MSRB I, Room 4510D, Ann Arbor, MI 48108, USA.
Miranda L SimesDepartment of Pathology, University of Michigan, 1150 West Medical Center Dr, MSRB I, Room 4510D, Ann Arbor, MI 48108, USA.
Sidney WeaverDepartment of Pathology, University of Michigan, 1150 West Medical Center Dr, MSRB I, Room 4510D, Ann Arbor, MI 48108, USA.
Hyo Je ChoDepartment of Pathology, University of Michigan, 1150 West Medical Center Dr, MSRB I, Room 4510D, Ann Arbor, MI 48108, USA.
Alexandrea RizoDepartment of Pathology, University of Michigan, 1150 West Medical Center Dr, MSRB I, Room 4510D, Ann Arbor, MI 48108, USA.
Sergey ZolovDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2670, USA.
Venkateshwar G KeshamouniDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2670, USA.
Jolanta GrembeckaDepartment of Pathology, University of Michigan, 1150 West Medical Center Dr, MSRB I, Room 4510D, Ann Arbor, MI 48108, USA. Electronic address: jolantag@umich.edu.
Tomasz CierpickiDepartment of Pathology, University of Michigan, 1150 West Medical Center Dr, MSRB I, Room 4510D, Ann Arbor, MI 48108, USA. Electronic address: tomaszc@umich.edu.
University of Michigan · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2M
Development of novel anti-leukemia agents targeting the menin-MLL interactionR01CA160467 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GREMBECKA, JOLANTA · 2011 to 2021
$3.4M
Development of ASH1L inhibitors for acute leukemiaR01CA244254 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GREMBECKA, JOLANTA · 2020 to 2024
$2.8M
Targeting NSD1 in leukemiaR01CA226759 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CIERPICKI, TOMASZ · 2019 to 2023
$2.3M
Development of small molecules targeting Ring1B-Bmi1 E3 ligase in leukemiaR01CA207272 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CIERPICKI, TOMASZ · 2016 to 2020
$2.0M
Targeting epigenetic reader GAS41R01CA240514 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CIERPICKI, TOMASZ · 2020 to 2023
$2.0M
Targeting protein-protein interactions of Bmi1 oncoproteinR01CA201204 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GREMBECKA, JOLANTA · 2016 to 2018
$959k
NCI NIH HHS P30 CA046592NCI NIH HHS R01 CA160467NCI NIH HHS R01 CA201204NCI NIH HHS R01 CA207272NCI NIH HHS R01 CA226759NCI NIH HHS R01 CA240514NCI NIH HHS R01 CA244254
6 · The paper itself

Abstract

GAS41 is an emerging oncogene overexpressed and implicated in multiple cancers, including non-small cell lung cancer (NSCLC). GAS41 is a dimeric protein that contains the YEATS domain, which is involved in the recognition of lysine-acylated histones. Here, we report the development of GAS41 YEATS inhibitors by employing a fragment-based screening approach. These inhibitors bind to GAS41 YEATS domain in a channel constituting a recognition site for acylated lysine on histone proteins. To enhance inhibitory activity, we developed a dimeric analog with nanomolar activity that blocks interactions of GAS41 with acetylated histone H3. Our lead compound engages GAS41 in cells, blocks proliferation of NSCLC cells, and modulates expression of GAS41-dependent genes, validating on-target mechanism of action. This study demonstrates that disruption of GAS41 protein-protein interactions may represent an attractive approach to target lung cancer cells. This work exemplifies the use of bivalent inhibitors as a general strategy to block challenging protein-protein interactions.

Indexed as

AmidesAntineoplastic AgentsCarcinoma, Non-Small-Cell LungCell ProliferationCells, CulturedDrug Screening Assays, AntitumorFemaleHumansLung NeoplasmsMaleMolecular StructureProtein Interaction Domains and MotifsThiophenesTranscription FactorsAmidesAntineoplastic AgentsThiophenesTranscription FactorsYEATS4 protein, humanchemical probesdimeric inhibitorsGAS41lung cancerYEATS domain

Identifiers

PMID34289376
PMCPMC8923076
OpenAlexW3185358011

What OpenQuestion holds

Textmetadata
LicenceTDM
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.