Evidence map›Paper›PMID 38328231›Full record

ArticlebioRxiv : the preprint server for biology2024

Identification of CK2α' selective inhibitors by the screening of an allosteric-kinase-inhibitor-like compound library.

Deepti Mudaliar, Rachel H Mansky, Angel White, Grace Baudhuin, Jon Hawkinson, Henry Wong, Michael A Walters, Rocio Gomez-Pastor

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

Article in bioRxiv : the preprint server for biology, 2024. 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, 0 citations in OpenAlex.

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

8 authors at 1 institution in 1 country.

Deepti MudaliarDepartment of Medicinal Chemistry, Institute for Therapeutics Discovery and Development, University of Minnesota, Minneapolis, Minnesota 55414, United States.
Rachel H ManskyDepartment of Neuroscience, University of Minnesota, School of Medicine, Minneapolis, Minnesota 55414, United States.
Angel WhiteDepartment of Neuroscience, University of Minnesota, School of Medicine, Minneapolis, Minnesota 55414, United States.ORCID 0000-0001-8039-3542
Grace BaudhuinDepartment of Neuroscience, University of Minnesota, School of Medicine, Minneapolis, Minnesota 55414, United States.
Jon HawkinsonDepartment of Medicinal Chemistry, Institute for Therapeutics Discovery and Development, University of Minnesota, Minneapolis, Minnesota 55414, United States.ORCID 0000-0001-5461-7071
Henry WongDepartment of Medicinal Chemistry, Institute for Therapeutics Discovery and Development, University of Minnesota, Minneapolis, Minnesota 55414, United States.ORCID 0000-0003-1755-1485
Michael A WaltersDepartment of Medicinal Chemistry, Institute for Therapeutics Discovery and Development, University of Minnesota, Minneapolis, Minnesota 55414, United States.ORCID 0000-0001-5650-9277
Rocio Gomez-PastorDepartment of Neuroscience, University of Minnesota, School of Medicine, Minneapolis, Minnesota 55414, United States.ORCID 0000-0003-1136-5462
University of Minnesota · US

Funding

Chemical Probes as Allosteric Modulators of CK2 Alpha Prime Targeting Huntington's DiseaseR21NS116260 · NINDS · UNIVERSITY OF MINNESOTA · PI GOMEZ-PASTOR, ROCIO · 2021 to 2022
$417k
NINDS NIH HHS R21 NS116260
6 · The paper itself

Abstract

Protein Kinase CK2 is a holoenzyme composed of two regulatory subunits (CK2β) and two catalytic subunits (CK2α and CK2α'). CK2 controls several cellular processes including proliferation, inflammation, and cell death. However, CK2α and CK2α' possess different expression patterns and substrates and therefore impact each of these processes differently. Elevated CK2α participates in the development of cancer, while increased CK2α' has been associated with neurodegeneration, especially Huntington's disease (HD). HD is a fatal disease for which no effective therapies are available. Genetic deletion of CK2α' in HD mouse models has ameliorated neurodegeneration. Therefore, pharmacological inhibition of CK2α' presents a promising therapeutic strategy for treating HD. However, current CK2 inhibitors are unable to discriminate between CK2α and CK2α' due to their high structural homology, especially in the targeted ATP binding site. Using computational analyses, we found a potential Type IV ("D" pocket) allosteric site on CK2α' that contained different residues than CK2α and was distal from the ATP binding pocket featured in both kinases. With this potential allosteric site in mind, we screened a commercial library containing ~29,000 allosteric-kinase-inhibitor-like compounds using a CK2α' activity-dependent ADP-Glo

Indexed as

allosteric inhibitorsCK2α’CX-4945Huntington’s diseasekinase inhibitorsneurodegeneration

Identifiers

PMID38328231
PMCPMC10849513
OpenAlexW4391104507

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.