Evidence map›Paper›PMID 39386645›Full record

ArticlebioRxiv : the preprint server for biology2024

Discovery of electrophilic degraders that exploit S

Zhe Zhuang, Woong Sub Byun, Zuzanna Kozicka, Brendan G Dwyer, Katherine A Donovan, Zixuan Jiang, Hannah M Jones, Dinah M Abeja, Meredith N Nix, Jianing Zhong and 4 more

Abstract 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.

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

14 authors.

Zhe ZhuangDepartment of Chemical and Systems Biology, ChEM-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, CA, USA.ORCID 0000-0001-6679-0496
Woong Sub ByunDepartment of Chemical and Systems Biology, ChEM-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, CA, USA.ORCID 0000-0003-4676-3698
Zuzanna KozickaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Brendan G DwyerDepartment of Chemical and Systems Biology, ChEM-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, CA, USA.
Katherine A DonovanDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Zixuan JiangDepartment of Chemistry, Stanford University, Stanford, CA, USA.ORCID 0009-0008-8167-4918
Hannah M JonesDepartment of Chemical and Systems Biology, ChEM-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, CA, USA.
Dinah M AbejaDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Meredith N NixDepartment of Chemistry, Stanford University, Stanford, CA, USA.
Jianing ZhongDepartment of Chemistry, Stanford University, Stanford, CA, USA.
Mikołaj SłabickiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Eric S FischerDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Benjamin L EbertDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nathanael S GrayDepartment of Chemical and Systems Biology, ChEM-H, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Stanford, CA, USA.

Funding

TYROSINE KINASE ONCOGENESIS IN MYELOID LEUKEMIAP01CA066996 · NCI · DANA-FARBER CANCER INSTITUTE · PI SCOTT A ARMSTRONG · 1996 to 2026
$52.5M
The role of clonal hematopoiesis in the development and therapy of myeloid malignanciesR35CA253125 · NCI · DANA-FARBER CANCER INST · PI EBERT, BENJAMIN LEVINE · 2020 to 2024
$4.9M
Degrading therapeutically important kinases using small moleculesR01CA218278 · NCI · STANFORD UNIVERSITY · PI Eric Sebastian Fischer, NATHANAEL Schiander GRAY · 2019 to 2026
$4.6M
Development of a generalizable chemo-proteomics screening platform for small molecule degraders applied to HDACsR01CA262188 · NCI · DANA-FARBER CANCER INST · PI FISCHER, ERIC SEBASTIAN · 2022 to 2025
$1.8M
500 MHz NMR Spectrometer System with High Sensitivity Cryoprobe and Automated Sample Changer for Biochemical ResearchS10OD028697 · OD · STANFORD UNIVERSITY · PI BURNS, NOAH ZACHARY · 2020 to 2020
$709k
NCI NIH HHS P01 CA066996NCI NIH HHS R01 CA218278NCI NIH HHS R01 CA262188NCI NIH HHS R35 CA253125NIH HHS S10 OD028697
6 · The paper itself

Abstract

Targeted covalent inhibition (TCI) and targeted protein degradation (TPD) have proven effective in pharmacologically addressing formerly 'undruggable' targets. Integration of both methodologies has resulted in the development of electrophilic degraders where recruitment of a suitable E3 ubiquitin ligase is achieved through formation of a covalent bond with a cysteine nucleophile. Expanding the scope of electrophilic degraders requires the development of electrophiles with tempered reactivity that enable selective ligase recruitment and reduce cross-reactivity with other cellular nucleophiles. In this study, we report the use of chemical moieties that enable nucleophilic aromatic substitution (S

Identifiers

PMID39386645
PMCPMC11463635

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.