Evidence map›Paper›PMID 40060528›Full record

ArticlebioRxiv : the preprint server for biology2025

Sulfinyl Aziridines as Stereoselective Covalent Destabilizing Degraders of the Oncogenic Transcription Factor MYC.

Hannah T Rosen, Kelvin Li, Erin L Li, Brynne Currier, Scott M Brittain, Francisco J Garcia, Diana C Beard, Sandra Haenni-Holzinger, Dustin Dovala, Jeffrey M McKenna and 3 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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

13 authors.

Hannah T RosenDepartment of Chemistry, University of California, Berkeley, Berkeley, CA 94720 USA.
Kelvin LiDepartment of Chemistry, University of California, Berkeley, Berkeley, CA 94720 USA.
Erin L LiDepartment of Chemistry, University of California, Berkeley, Berkeley, CA 94720 USA.
Brynne CurrierDepartment of Chemistry, University of California, Berkeley, Berkeley, CA 94720 USA.
Scott M BrittainNovartis-Berkeley Translational Chemical Biology Institute, Berkeley, CA 94720 USA.
Francisco J GarciaNovartis-Berkeley Translational Chemical Biology Institute, Berkeley, CA 94720 USA.
Diana C BeardNovartis-Berkeley Translational Chemical Biology Institute, Berkeley, CA 94720 USA.
Sandra Haenni-HolzingerNovartis-Berkeley Translational Chemical Biology Institute, Berkeley, CA 94720 USA.
Dustin DovalaNovartis-Berkeley Translational Chemical Biology Institute, Berkeley, CA 94720 USA.
Jeffrey M McKennaNovartis-Berkeley Translational Chemical Biology Institute, Berkeley, CA 94720 USA.
Markus SchirleNovartis-Berkeley Translational Chemical Biology Institute, Berkeley, CA 94720 USA.
Thomas J MaimoneDepartment of Chemistry, University of California, Berkeley, Berkeley, CA 94720 USA.
Daniel K NomuraDepartment of Chemistry, University of California, Berkeley, Berkeley, CA 94720 USA.ORCID 0000-0003-1614-8360

Funding

Chemical Approaches to Modulate PAX3-FOXO1 in Fusion-Positive Alveolar RhabdomyosarcomaUM1CA294108 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ALEX B BURGIN, Alexandra E Gould · 2024 to 2026
$6.9M
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 CA263814NCI NIH HHS UM1 CA294108NIH HHS S10 OD018174NIH HHS S10 OD024998
6 · The paper itself

Abstract

While MYC is a significant oncogenic transcription factor driver of cancer, directly targeting MYC has remained challenging due to its intrinsic disorder and poorly defined structure, deeming it "undruggable." Whether transient pockets formed within intrinsically disordered and unstructured regions of proteins can be selectively targeted with small molecules remains an outstanding challenge. Here, we developed a bespoke stereochemically-paired spirocyclic oxindole aziridine covalent library and screened this library for degradation of MYC. Through this screen, we identified a hit covalent ligand KL2-236, bearing a unique sulfinyl aziridine warhead, that engaged MYC

Indexed as

activity-based protein profilingcancerchemoproteomicscovalentcysteineintrinsically disorderedMYCsulfinyl aziridinetargeted protein degradation

Identifiers

PMID40060528
PMCPMC11888305

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.