Evidence map›Paper›PMID 42006253›Full record

ArticleACS bio & med chem Au2026

Discovery of Small-Molecule Antagonists of PHF1 and 19 Demonstrates the Ligandability of PRC2 Accessory Proteins.

Isabelle E Amick, Rebecca L Johnson, Jiuyang Liu, Cameron R Bussey-Sutton, Ikeer Y Mancera-Ortiz, Jacqueline L Norris-Drouin, Shelton R Boyd, Stephanie H Cholensky, Cathy J Spangler, Robert K McGinty and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS bio & med chem Au, 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

14 authors.

Isabelle E AmickCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.ORCID https://orcid.org/0000-0001-7876-4842
Rebecca L JohnsonCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Jiuyang LiuDepartment of Pharmacology, University of Colorado School of Medicine, Aurora, Colorado 80045, United States.
Cameron R Bussey-SuttonDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Ikeer Y Mancera-OrtizCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
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 at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Shelton R BoydCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.ORCID https://orcid.org/0000-0002-1098-378X
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 at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Cathy J SpanglerDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Robert K McGintyDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.ORCID https://orcid.org/0000-0001-9641-7350
Brian D StrahlDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.ORCID https://orcid.org/0000-0002-4947-6259
Tatiana G KutateladzeDepartment of Pharmacology, University of Colorado School of Medicine, Aurora, Colorado 80045, United States.ORCID https://orcid.org/0000-0001-7375-6990
Stephen V FryeCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.ORCID https://orcid.org/0000-0002-2415-2215
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 at Chapel Hill, Chapel Hill, North Carolina 27599, United States.ORCID https://orcid.org/0000-0002-6034-7116

Funding

Mechanisms of chromatin and transcriptional regulationR35GM126900 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Brian D Strahl · 2018 to 2026
$5.5M
NIGMS NIH HHS R35 GM126900
6 · The paper itself

Abstract

PHF1 and PHF19 are key accessory components of polycomb repressive complex 2 (PRC2) which is responsible for trimethylation at histone H3 lysine 27, ultimately leading to gene repression. PHF1 and 19 are known for their methyl-lysine reader Tudor domains that recognize methylated lysine 36 on H3, and they have also been implicated as drivers of a range of cancers, including multiple myeloma. Here, we describe the first small-molecule antagonist of the Tudor domains of PHF1 and 19. We screened an internal library of ∼ 1 K compounds against the Tudor domains using a TR-FRET assay. Upon validation of a hit compound, we performed structure-activity relationship (SAR) studies to better understand the binding mode and improve the affinity of the compound for the PHF1 and 19 Tudor domains. One such compound, UNC7242, which binds PHF1 with a

Indexed as

antagonistmethyl-lysine readerplant homeodomain finger proteinspolycomb repressive complex 2Tudor domain

Identifiers

PMID42006253
PMCPMC13087805

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.