Evidence map›Paper›PMID 34174168›Full record

ArticleChemMedChem2021

Polycomb Paralog Chromodomain Inhibitors Active against Both CBX6 and CBX8*.

Natalia Milosevich, Chelsea R Wilson, Tyler M Brown, Aktan Alpsoy, Sijie Wang, Katelyn E Connelly, Kirsten A D Sinclair, Felino R Ponio, Rebecca Hof, Emily C Dykhuizen and 1 more

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

Article in ChemMedChem, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.6field-weighted citation impact, top 36% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

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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

11 authors at 2 institutions in 2 countries.

Natalia MilosevichDepartment of Chemistry, University of Victoria, Victoria, BC, V8W 3V6, Canada.ORCID 0000-0001-5708-6907
Chelsea R WilsonDepartment of Chemistry, University of Victoria, Victoria, BC, V8W 3V6, Canada.ORCID 0000-0001-6743-715X
Tyler M BrownDepartment of Chemistry, University of Victoria, Victoria, BC, V8W 3V6, Canada.
Aktan AlpsoyDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University and Purdue University Center for Cancer Research, 575 Stadium Mall Drive, West Lafayette, IN, 47906, USA.ORCID 0000-0002-8940-8277
Sijie WangDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University and Purdue University Center for Cancer Research, 575 Stadium Mall Drive, West Lafayette, IN, 47906, USA.
Katelyn E ConnellyDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University and Purdue University Center for Cancer Research, 575 Stadium Mall Drive, West Lafayette, IN, 47906, USA.ORCID 0000-0002-1693-5519
Kirsten A D SinclairDepartment of Chemistry, University of Victoria, Victoria, BC, V8W 3V6, Canada.
Felino R PonioDepartment of Chemistry, University of Victoria, Victoria, BC, V8W 3V6, Canada.
Rebecca HofDepartment of Chemistry, University of Victoria, Victoria, BC, V8W 3V6, Canada.ORCID 0000-0002-0265-2307
Emily C DykhuizenDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University and Purdue University Center for Cancer Research, 575 Stadium Mall Drive, West Lafayette, IN, 47906, USA.ORCID 0000-0003-3072-1469
Fraser HofDepartment of Chemistry, University of Victoria, Victoria, BC, V8W 3V6, Canada.ORCID 0000-0003-4658-9132
University of Victoria · CAPurdue University West Lafayette · US

Funding

The tumor suppressive role of PBRM1, the bromodomain-containing subunit of the PBAF chromatin remodeling complexU01CA207532 · NCI · PURDUE UNIVERSITY · PI DYKHUIZEN, EMILY CARLA · 2017 to 2021
$1.7M
Canada Research Chairs programCanadian Cancer Society Research Institute 703789NCI NIH HHS U01 CA207532Prostate Cancer Foundation of British ColumbiaUS National Institutes of Health U01CA207532
6 · The paper itself

Abstract

Methyllysine reader proteins bind to methylated lysine residues and alter gene transcription by changing either the compaction state of chromatin or by the recruitment of other multiprotein complexes. The polycomb paralog family of methyllysine readers bind to trimethylated lysine on the tail of histone 3 (H3) via a highly conserved aromatic cage located in their chromodomains. Each of the polycomb paralogs are implicated in several disease states. CBX6 and CBX8 are members of the polycomb paralog family with two structurally similar chromodomains. By exploring the structure-activity relationships of a previously reported CBX6 inhibitor we have discovered more potent and cell permeable analogs. Our current report includes potent, dual-selective inhibitors of CBX6 and CBX8. We have shown that the -2 position in our scaffold is an important residue for selectivity amongst the polycomb paralogs. Preliminary cell-based studies show that the new inhibitors impact cell proliferation in a rhabdoid tumor cell line.

Indexed as

Antineoplastic AgentsCell LineCell ProliferationDose-Response Relationship, DrugDrug Screening Assays, AntitumorHumansLigandsMolecular StructurePeptidesPolycomb-Group ProteinsPolycomb Repressive Complex 1Structure-Activity RelationshipAntineoplastic Agentscbx6 protein, humanCBX8 protein, humanLigandsPeptidesPolycomb-Group ProteinsPolycomb Repressive Complex 1CBX6CBX8CBX inhibitorsMethyllysine reader proteinspolycomb paralogs

Identifiers

PMID34174168
PMCPMC8497432
OpenAlexW3176203625

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.