Evidence map›Paper›PMID 40666473›Full record

ArticleACS medicinal chemistry letters2025

Exploring the Ligandability of 53BP1 through Fragment-Based Approaches.

Beatrice Chiew, Menachem J Gunzburg, Caroline A Foley, Hong Zeng, Aiping Dong, Peter J Brown, Juliana The, Jacqueline L Norris-Drouin, Stephanie H Cholensky, Biswaranjan Mohanty and 4 more

Abstract read
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In one paragraph

Article in ACS medicinal chemistry letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

14 authors.

Beatrice ChiewMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
Menachem J GunzburgMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
Caroline A FoleyMonash Fragment Platform, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.ORCID https://orcid.org/0000-0003-4888-9948
Hong ZengStructural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada, M5G 1L7.
Aiping DongStructural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada, M5G 1L7.
Peter J BrownStructural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada, M5G 1L7.
Juliana TheStructural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada, M5G 1L7.
Jacqueline L Norris-DrouinCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.
Stephanie H CholenskyCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.
Biswaranjan MohantyMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.ORCID https://orcid.org/0000-0002-6921-343X
Martin J ScanlonMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.ORCID https://orcid.org/0000-0002-9230-7506
Stephen J HeadeyMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
Bradley C DoakMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.ORCID https://orcid.org/0000-0001-8422-675X
Lindsey I JamesCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.ORCID https://orcid.org/0000-0002-6034-7116

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

53BP1 is a DNA damage response protein recruited to sites of double strand breaks through recognition of dimethylated lysine on histone 4 by its tandem Tudor domains. Like 53BP1, BRCA-1 plays a role in the regulation of DNA repair pathways, and BRCA-1 mutations have been strongly linked to breast and ovarian cancer. Interestingly, mice null for 53BP1 and BRCA-1 genes display minimal tumor formation, suggesting that the effects of deleterious BRCA-1 mutations could be prevented with potent 53BP1 small molecule antagonists. Herein, we describe a fragment screen that was used to identify compounds that bind to the 53BP1 Tudor domain and a chemoinformatic workflow to select near-neighbor analogues and establish structure activity relationships for these binders. The marked affinity improvements of the analogues over their parent fragments highlights the developability of these series and the utility of this approach in discovering novel hit compounds for 53BP1 and other methyl-lysine reader proteins.

Indexed as

53BP1chemoinformaticsepigeneticsfragment-based drug designfragment screeningnuclear magnetic resonancesurface plasmon resonance

Identifiers

PMID40666473
PMCPMC12257399

What OpenQuestion holds

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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.