Evidence map›Paper›PMID 42202785›Full record

ArticleCell chemical biology2026

The molecular basis for nuclear pore destruction by a proximity-inducing molecular glue.

Stephen M Hinshaw, Linjie Yuan, Md Abdullah Al Noman, Michael J Martinez, Gianna M Colombo, Brendan G Dwyer, Wenzhi Ji, Bryan A Romero, Ines Forrest, Joey Lu and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2026. 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.

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

17 authors.

Stephen M HinshawDepartment of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA. Electronic address: hinshaw@stanford.edu.
Linjie YuanDepartment of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA; Department of Medicine, Division of Oncology, Stanford School of Medicine, Stanford, CA 94305, USA.
Md Abdullah Al NomanDepartment of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA.
Michael J MartinezDepartment of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA.
Gianna M ColomboDepartment of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA; Department of Medicine, Division of Oncology, Stanford School of Medicine, Stanford, CA 94305, USA.
Brendan G DwyerDepartment of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA.
Wenzhi JiDepartment of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA.
Bryan A RomeroDepartment of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA.
Ines ForrestDepartment of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA.
Joey LuDepartment of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA; Department of Medicine, Division of Oncology, Stanford School of Medicine, Stanford, CA 94305, USA.
Jing BianDepartment of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA; Department of Medicine, Division of Oncology, Stanford School of Medicine, Stanford, CA 94305, USA.
Trae B DunnDepartment of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA.
Ethan R GarvinDepartment of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA; Department of Medicine, Division of Oncology, Stanford School of Medicine, Stanford, CA 94305, USA; Department of Genetics, Stanford School of Medicine, Stanford, CA 94305, USA.
Daniel FernandezMacromolecular Structure, Nucleus at Sarafan ChEM-H, Stanford University, Stanford, CA 94305, USA.
Tinghu ZhangDepartment of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA.
Nathanael S GrayDepartment of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA.
Steven M CorselloDepartment of Chemical and Systems Biology, Stanford School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA; Department of Medicine, Division of Oncology, Stanford School of Medicine, Stanford, CA 94305, USA. Electronic address: corsello@stanford.edu.

Funding

A Synchrotron Radiation Structural Biology ResourcesP30GM133894 · NIGMS · STANFORD UNIVERSITY · PI Aina E. Cohen, KEITH O HODGSON · 2020 to 2026
$43.3M
NIGMS NIH HHS P30 GM133894
6 · The paper itself

Abstract

Molecular glues that induce new protein interactions can be potent therapeutics. We and others recently discovered that the small molecule PRLX-93936 (PRLX), which was originally developed as an erastin derivative with antitumor activity, is a molecular glue that alters the substrate specificity of the TRIM21 ubiquitin ligase. PRLX causes TRIM21 to bind the nuclear pore protein NUP98, triggering nuclear pore complex (NPC) degradation. We present here the structural and biochemical basis of NUP98 recognition, finding that ternary complex assembly depends on the creation of a composite TRIM21-small molecule surface competent for NUP98 binding. A scarcity of direct small molecule-NUP98 contacts likely explains how multiple structurally diverse TRIM21 ligands can induce NPC degradation. We also report the discovery of an enhanced molecular glue, MAN-021, and describe its structure. Our findings provide a basis for rational development of next-generation small molecules with enhanced or differentiated activities.

Indexed as

Nuclear PoreNuclear Pore Complex ProteinsSmall Molecule LibrariesHumansModels, MolecularProtein BindingTRIM21 ProteinNuclear Pore Complex ProteinsSmall Molecule LibrariesTRIM21 Proteincrystal structuredrug discoveryE3 ligasemolecular glueNUP98ternary complexTRIM21

Identifiers

PMID42202785
PMCPMC13361186

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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.