Evidence map›Paper›PMID 42174376›Full record

ArticleChemMedChem2026

Development of a Lysine-Reactive Targeted Covalent Inhibitor for the P300/CBP-Associated Factor Bromodomain Through Structure-Based Design.

Richard R Ede, Kerstin E Peterson, Richard K Begyinah, Irin P Tom, Jason M Ochoada, Molly S Sneddon, Ana Katrina Y Tiu, Marcus Fischer, Anang A Shelat, William C K Pomerantz

Abstract read
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In one paragraph

Article in ChemMedChem, 2026. 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
–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

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

10 authors.

Richard R EdeDepartment of Chemistry, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0003-1858-6823
Kerstin E PetersonDepartment of Chemistry, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0002-0291-4039
Richard K BegyinahDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Irin P TomDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Jason M OchoadaDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID 0000-0003-0728-8820
Molly S SneddonDepartment of Chemistry, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0002-7249-3401
Ana Katrina Y TiuDepartment of Chemistry, University of Minnesota, Minneapolis, Minnesota, USA.
Marcus FischerDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID 0000-0002-7179-2581
Anang A ShelatDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID 0000-0002-6266-2910
William C K PomerantzDepartment of Chemistry, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0002-0163-4078

Funding

Training the Next Generation of Chemical BiologistsT32GM132029 · NIGMS · UNIVERSITY OF MINNESOTA · PI Erin Elizabeth Carlson, William Charles Krause Pomerantz · 2019 to 2026
$2.7M
Chemical Probe Development for Epigenetic Complexes Enabled by Protein-Observed 19F NMRR35GM140837 · NIGMS · UNIVERSITY OF MINNESOTA · PI William Charles Krause Pomerantz · 2021 to 2026
$2.5M
Targeting the chromatin binding domains of BPTF for neuroblastoma epigenetic therapyR01CA290805 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Marcus Fischer, William Charles Krause Pomerantz · 2025 to 2026
$1.5M
American Lebanese Syrian Associated Charities (ALSAC)NCI NIH HHS R01 CA290805NIGMS NIH HHS R35 GM140837NIGMS NIH HHS T32 GM132029NIH HHS R01CA290805NIH HHS R35GM140837NIH HHS T32GM132029NSF GRFP
6 · The paper itself

Abstract

Epigenetics is defined by changes in heritable phenotypes that do not involve a change in DNA sequence. P300/CBP-associated factor (PCAF) is an important epigenetic regulatory protein that can alter chromatin through a histone acetyltransferase domain, while also serving as an epigenetic reader through a C-terminal bromodomain. PCAF promotes the transcription of the HIV-1 genome and is implicated in the development of glioblastoma. The currently reported PCAF inhibitors are non-covalent and require high concentration to maintain target occupancy. Here, we explore a new approach using covalent inhibition. Starting with a lead scaffold (BZ1), test-molecules were rationally designed for selectively targeting PCAF by installing lysine-reactive groups onto the lead scaffold to enable covalent bond formation with the nonconserved lysine residue in the PCAF bromodomain. The inhibition, selectivity, and kinetic properties (k

Indexed as

Drug DesignLysinep300-CBP Transcription FactorsDose-Response Relationship, DrugHumansMolecular Structurep300-CBP-Associated FactorProtein DomainsStructure-Activity RelationshipLysinep300-CBP-Associated Factorp300-CBP Transcription Factorscovalent inhibitorsdrug discoveryKAT2Blysine‐reactivep300/CBP‐associated factor

Identifiers

PMID42174376
PMCPMC13206289

What Socratic 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 Socratic graph.