Evidence map›Paper›PMID 39691404›Full record

ArticleRSC medicinal chemistry2025

Exploiting the DCAF16-SPIN4 interaction to identify DCAF16 ligands for PROTAC development.

Isabella A Riha, Miguel A Campos, Xiaokang Jin, Fiona Y Wang, Chenlu Zhang, Sara F Dunne, Benjamin F Cravatt, Xiaoyu Zhang

Abstract read
In one paragraph

Article in RSC medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
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.

Isabella A RihaDepartment of Chemistry, Northwestern University Evanston IL 60208 USA zhang@northwestern.edu.ORCID https://orcid.org/0009-0000-1278-498X
Miguel A CamposDepartment of Chemistry, Northwestern University Evanston IL 60208 USA zhang@northwestern.edu.
Xiaokang JinDepartment of Chemistry, Northwestern University Evanston IL 60208 USA zhang@northwestern.edu.
Fiona Y WangDepartment of Chemistry, Northwestern University Evanston IL 60208 USA zhang@northwestern.edu.
Chenlu ZhangDepartment of Chemistry, Northwestern University Evanston IL 60208 USA zhang@northwestern.edu.ORCID https://orcid.org/0000-0003-4171-5099
Sara F DunneHigh Throughput Analysis Laboratory, Northwestern University Evanston IL 60208 USA.
Benjamin F CravattDepartment of Chemistry, The Scripps Research Institute La Jolla CA 92037 USA.ORCID https://orcid.org/0000-0001-5330-3492
Xiaoyu ZhangDepartment of Chemistry, Northwestern University Evanston IL 60208 USA zhang@northwestern.edu.ORCID https://orcid.org/0000-0002-0951-9664

Funding

Chemistry of Life Processes Predoctoral Training ProgramT32GM149439 · NIGMS · NORTHWESTERN UNIVERSITY · PI NEIL L KELLEHER · 2023 to 2026
$1.6M
Discovery of small molecule-mediated protein degradation pathways in human cancerR00CA248715 · NCI · NORTHWESTERN UNIVERSITY · PI ZHANG, XIAOYU · 2022 to 2024
$747k
NCI NIH HHS R00 CA248715NIGMS NIH HHS T32 GM149439
6 · The paper itself

Abstract

Traditional small molecule drugs often target protein activity directly, but challenges arise when proteins lack suitable functional sites. An alternative approach is targeted protein degradation (TPD), which directs proteins to cellular machinery for proteolytic degradation. Recent studies have identified additional E3 ligases suitable for TPD, expanding the potential of this approach. Among these, DCAF16 has shown promise in facilitating protein degradation through both PROTAC and molecular glue mechanisms. In this study, we developed a homogeneous time resolved fluorescence (HTRF) assay to discover new DCAF16 binders. Using an in-house electrophile library, we identified two diastereomeric compounds, with one engaging DCAF16 at cysteines C177-179 and another reducing its expression. We demonstrated that the compound covalently engaging DCAF16 can be transformed into a PROTAC capable of degrading FKBP12.

Identifiers

PMID39691404
PMCPMC11647575

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Registered trials

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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.