Evidence map›Paper›PMID 41302507›Full record

ArticleMolecules (Basel, Switzerland)2025

Design and Synthesis of Novel Candidate CK1δ Proteolysis Targeting Chimeras (PROTACs).

Malte Arnold, Temi Thompson, Lorraine Glennie, Mattes Hollnagel, Gopal Sapkota, Christian Peifer

Abstract read
In one paragraph

Article in Molecules (Basel, Switzerland), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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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

6 authors.

Malte ArnoldInstitute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry, Christian-Albrechts-University of Kiel, 24118 Kiel, Germany.ORCID 0009-0009-5352-8515
Temi ThompsonMRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
Lorraine GlennieMRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
Mattes HollnagelInstitute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry, Christian-Albrechts-University of Kiel, 24118 Kiel, Germany.
Gopal SapkotaMRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.ORCID 0000-0001-9931-3338
Christian PeiferInstitute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry, Christian-Albrechts-University of Kiel, 24118 Kiel, Germany.ORCID 0000-0003-1532-7826

Funding

UKRI Medical Research Council MC_UU_00038/6
6 · The paper itself

Abstract

The dysregulation of CK1 isoforms is linked to various types of diseases, including neurodegeneration and different types of neoplasia such as colon, pancreatic, breast, and ovarian cancer. For CK1 isoforms, a plethora of effective small molecule inhibitors are available. However, only a few degraders of CK1α and, more recently, proteolysis targeting chimeras (PROTACs) for CK1δ/CK1ε have been reported. In this study, we applied the PROTAC concept by harnessing molecular modelling to design and synthesize a series of candidate CK1δ-targeting PROTACs based on a highly specific and potent benzothiazole-based CK1δ inhibitor that we previously developed in our lab. In the present study, we established a modular synthetic platform to systematically generate a set of PROTAC degrader candidates consisting of the CK1δ-specific inhibitor scaffold, alkyl and PEG linker motifs with various lengths, and Cereblon (CRBN)-engaging pomalidomide and thalidomide derivatives as E3 ligase binders. We demonstrate that several PROTACs degrade CK1δ/ε in various cells. The most potent PROTAC

Indexed as

Casein Kinase IdeltaDrug DesignProteolysisAdaptor Proteins, Signal TransducingBenzothiazolesHumansModels, MolecularPhosphorylationProteasome Endopeptidase ComplexProteolysis Targeting ChimeraThalidomideUbiquitin-Protein LigasesAdaptor Proteins, Signal TransducingBenzothiazolesCasein Kinase IdeltaCRBN protein, humanProteasome Endopeptidase ComplexProteolysis Targeting ChimeraThalidomideUbiquitin-Protein Ligasescancer therapyCK1δkinasesPROTACsprotein degradation

Identifiers

PMID41302507
PMCPMC12655757

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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.