Evidence map›Paper›PMID 41867716›Full record

ArticlebioRxiv : the preprint server for biology2026

An Optimized RNF126-Targeting Covalent Handle for Molecular Glue Degraders.

Aman Modi, Ethan S Toriki, Christian E Stieger, Emily A Lau, Claire Song, Alyssa Chew, Amy Tsao, Kaila Nishikawa, Jeffrey McKenna, Daniel K Nomura

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for 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

5 · Who and what money

Authors and funding

10 authors.

Aman ModiDepartments of Chemistry and Molecular and Cell Biology, University of California, Berkeley, Berkeley, California USA 94720.
Ethan S TorikiDepartments of Chemistry and Molecular and Cell Biology, University of California, Berkeley, Berkeley, California USA 94720.
Christian E StiegerDepartments of Chemistry and Molecular and Cell Biology, University of California, Berkeley, Berkeley, California USA 94720.
Emily A LauDepartments of Chemistry and Molecular and Cell Biology, University of California, Berkeley, Berkeley, California USA 94720.
Claire SongDepartments of Chemistry and Molecular and Cell Biology, University of California, Berkeley, Berkeley, California USA 94720.
Alyssa ChewDepartments of Chemistry and Molecular and Cell Biology, University of California, Berkeley, Berkeley, California USA 94720.
Amy TsaoDepartments of Chemistry and Molecular and Cell Biology, University of California, Berkeley, Berkeley, California USA 94720.
Kaila NishikawaDepartments of Chemistry and Molecular and Cell Biology, University of California, Berkeley, Berkeley, California USA 94720.
Jeffrey McKennaNovartis-Berkeley Translational Chemical Biology Institute.
Daniel K NomuraDepartments of Chemistry and Molecular and Cell Biology, University of California, Berkeley, Berkeley, California USA 94720.ORCID 0000-0003-1614-8360

Funding

Tackling Undruggable Cancer Targets using Chemoproteomic PlatformsR35CA263814 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI Daniel Nomura · 2022 to 2026
$4.6M
Harnessing E3 Ligases for Cancer TherapyR01CA240981 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI Daniel Nomura · 2019 to 2026
$4.3M
Pacific Biosciences PacBio RS Single Molecule Real Time SequencerS10OD018174 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI ROKHSAR, DANIEL SOLEYMAN · 2014 to 2014
$600k
Acquisition of a Cryoprobe and Related Accessories for a 600 MHz NMR Spectrometer to Support Health Research Activities at the University of California, BerkeleyS10OD024998 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI HARTWIG, JOHN F · 2018 to 2018
$265k
NCI NIH HHS R01 CA240981NCI NIH HHS R35 CA263814NIH HHS S10 OD018174NIH HHS S10 OD024998
6 · The paper itself

Abstract

Molecular glue degraders represent a powerful modality for targeting proteins that are refractory to traditional inhibition. However, rational design principles for molecular glue degraders remain poorly defined. Previously, we reported a chemistry-centric strategy to identify covalent degradative handles that, when appended to established ligands, convert non-degradative inhibitors into molecular glue degraders by engaging permissive E3 ligases. This effort identified a fumarate-based electrophilic handle that covalently modified the E3 ligase RNF126, enabling degradation of multiple protein targets when transplanted across diverse ligands. Despite its conceptual impact, the high intrinsic reactivity and cytotoxicity of the fumarate handle limited its translational utility. Here, we report the development of an optimized and metabolically stabilized RNF126-targeting covalent handle incorporating a

Identifiers

PMID41867716
PMCPMC13001483

What OpenQuestion holds

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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.