Evidence map›Paper›PMID 34255515›Full record

ArticleJournal of medicinal chemistry2021

Controlling Intramolecular Interactions in the Design of Selective, High-Affinity Ligands for the CREBBP Bromodomain.

Michael Brand, James Clayton, Mustafa Moroglu, Matthias Schiedel, Sarah Picaud, Joseph P Bluck, Anna Skwarska, Hannah Bolland, Anthony K N Chan, Corentine M C Laurin and 18 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Targeting lysine acetylation readers and writers.Nature reviews. Drug discovery · 2025
    Review
  6. Small Molecule Ligands of the BET-like Bromodomain,Journal of medicinal chemistry · 2023
    Article
  7. Bromodomain inhibitors and therapeutic applications.Current opinion in chemical biology · 2023
    Review
  8. Article
  9. Virtual Special Issue: Epigenetics 2022.ACS pharmacology & translational science · 2022
    Article
  10. Virtual Special Issue: Epigenetics 2022.ACS medicinal chemistry letters · 2022
    Article
  11. Review
  12. Article
  13. RSC chemical biology · 2021
    Review
  14. 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

28 authors.

Michael BrandDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.
James ClaytonDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.
Mustafa MorogluDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.
Matthias SchiedelDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.
Sarah PicaudNuffield Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 3TA, U.K.
Joseph P BluckDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.ORCID 0000-0001-9170-5919
Anna SkwarskaOxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, U.K.
Hannah BollandOxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, U.K.
Anthony K N ChanDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.ORCID 0000-0002-7091-1294
Corentine M C LaurinDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.
Amy R ScorahDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.
Larissa SeeDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.
Timothy P C RooneyDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.ORCID 0000-0001-6788-5526
Katrina H AndrewsDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.
Oleg FedorovNuffield Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 3TA, U.K.
Gabriella PerellDepartment of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, United States.
Prakriti KalraDepartment of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, United States.
Kayla B VinhDepartment of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, United States.
Wilian A CortopassiDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.
Pascal HeitelDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.
Kirsten E ChristensenDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.
Richard I CooperDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.ORCID 0000-0001-9651-6308
Robert S PatonDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.ORCID 0000-0002-0104-4166
William C K PomerantzDepartment of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, United States.ORCID 0000-0002-0163-4078
Philip C BigginDepartment of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, U.K.ORCID 0000-0001-5100-8836
Ester M HammondOxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, U.K.ORCID 0000-0002-2335-3146
Panagis FilippakopoulosNuffield Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 3TA, U.K.
Stuart J ConwayDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.ORCID 0000-0002-5148-117X

Funding

Biotechnology and Biological Sciences Research Council BB/M015157/1Biotechnology and Biological Sciences Research Council BB/S507003/1Medical Research Council MR/N009460/1Medical Research Council MR/N010051/1Wellcome TrustWellcome Trust 095751/Z/11/Z
6 · The paper itself

Abstract

CREBBP (CBP/KAT3A) and its paralogue EP300 (KAT3B) are lysine acetyltransferases (KATs) that are essential for human development. They each comprise 10 domains through which they interact with >400 proteins, making them important transcriptional co-activators and key nodes in the human protein-protein interactome. The bromodomains of CREBBP and EP300 enable the binding of acetylated lysine residues from histones and a number of other important proteins, including p53, p73, E2F, and GATA1. Here, we report a work to develop a high-affinity, small-molecule ligand for the CREBBP and EP300 bromodomains [(-)-OXFBD05] that shows >100-fold selectivity over a representative member of the BET bromodomains, BRD4(1). Cellular studies using this ligand demonstrate that the inhibition of the CREBBP/EP300 bromodomain in HCT116 colon cancer cells results in lowered levels of c-Myc and a reduction in H3K18 and H3K27 acetylation. In hypoxia (<0.1% O

Indexed as

Drug DesignBenzodiazepinonesCREB-Binding ProteinDose-Response Relationship, DrugE1A-Associated p300 ProteinHCT116 CellsHumansLigandsMolecular StructureSmall Molecule LibrariesStructure-Activity RelationshipBenzodiazepinonesCREB-Binding ProteinCREBBP protein, humanE1A-Associated p300 ProteinEP300 protein, humanLigandsSmall Molecule Libraries

Identifiers

PMID34255515
PMCPMC8311651

What OpenQuestion holds

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Registered trials

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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.