Evidence map›Paper›PMID 38559242›Full record

ArticlebioRxiv : the preprint server for biology2024

Orthogonal IMiD-Degron Pairs Induce Selective Protein Degradation in Cells.

Patrick J Brennan, Rebecca E Saunders, Mary Spanou, Marta Serafini, Liang Sun, Guillaume P Heger, Agnieszka Konopacka, Ryan D Beveridge, Laurie Gordon, Shenaz B Bunally and 9 more

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, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 5 institutions in 3 countries.

Patrick J BrennanDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford; Oxford, UK.
Rebecca E SaundersGSK, Medicines Research Centre; Stevenage, UK.
Mary SpanouPerkinElmer; Beaconsfield, UK.
Marta SerafiniDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford; Oxford, UK.
Liang SunChemical Biology Program, Memorial Sloan Kettering Cancer Center; New York, USA.
Guillaume P HegerGSK, Medicines Research Centre; Stevenage, UK.
Agnieszka KonopackaGSK, Medicines Research Centre; Stevenage, UK.
Ryan D BeveridgeVirus Screening Facility, Weatherall Institute of Molecular Medicine, University of Oxford; Oxford, UK.
Laurie GordonGSK, Medicines Research Centre; Stevenage, UK.
Shenaz B BunallyGSK, Medicines Research Centre; Stevenage, UK.
Aurore SaudemontGSK, Medicines Research Centre; Stevenage, UK.
Andrew B BenowitzGSK, Medicines Research Centre; Stevenage, UK.
Carlos Martinez-FleitesGSK, Medicines Research Centre; Stevenage, UK.
Markus A QueisserGSK, Medicines Research Centre; Stevenage, UK.
Heeseon AnChemical Biology Program, Memorial Sloan Kettering Cancer Center; New York, USA.ORCID 0000-0002-8518-4077
Charlotte M DeaneDepartment of Statistics, University of Oxford; Oxford, UK.ORCID 0000-0003-1388-2252
Michael M HannGSK, Medicines Research Centre; Stevenage, UK.ORCID 0000-0003-4360-9505
Lewis L BrayshawGSK, Medicines Research Centre; Stevenage, UK.ORCID 0000-0003-2696-736X
Stuart J ConwayDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford; Oxford, UK.ORCID 0000-0002-5148-117X
Age UK · GBUniversity of Oxford · GBMemorial Sloan Kettering Cancer Center · USUniversity of California, Los Angeles · USPerkinElmer (United Kingdom) · GB

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Immunomodulatory imide drugs (IMiDs) including thalidomide, lenalidomide, and pomalidomide, can be used to induce degradation of a protein of interest that is fused to a short zinc finger (ZF) degron motif. These IMiDs, however, also induce degradation of endogenous neosubstrates, including IKZF1 and IKZF3. To improve degradation selectivity, we took a bump-and-hole approach to design and screen bumped IMiD analogs against 8380 ZF mutants. This yielded a bumped IMiD analog that induces efficient degradation of a mutant ZF degron, while not affecting other cellular proteins, including IKZF1 and IKZF3. In proof-of-concept studies, this system was applied to induce efficient degradation of TRIM28, a disease-relevant protein with no known small molecule binders. We anticipate that this system will make a valuable addition to the current arsenal of degron systems for use in target validation.

Identifiers

PMID38559242
PMCPMC10979945
OpenAlexW4392894195

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.