Evidence map›Paper›PMID 37066279›Full record

ArticlebioRxiv : the preprint server for biology2023

Photoswitchable Molecular Glues Enable Optical Control of Transcription Factor Degradation.

Christopher J Arp, Martin Reynders, Vedagopuram Sreekanth, Praveen Kokkonda, Michele Pagano, Amit Choudhary, Dirk Trauner

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. 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, 2 citations in OpenAlex.

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

7 authors at 4 institutions in 1 country.

Christopher J ArpDepartment of Chemistry, New York University, 100 Washington Sq E, New York, New York 10003, United States.
Martin ReyndersDepartment of Chemistry, New York University, 100 Washington Sq E, New York, New York 10003, United States.
Vedagopuram SreekanthChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, United States.
Praveen KokkondaChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, United States.
Michele PaganoDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, United States.
Amit ChoudharyChemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, United States.
Dirk TraunerDepartment of Chemistry, University of Pennsylvania, College of Arts and Sciences, 231 South 34 Street, Philadelphia, PA 19104-6323, United States.
Broad Institute · USNew York University · USHoward Hughes Medical Institute · USUniversity of the Sciences · US

Funding

Regulation of the cell proliferation by CRL ubiquitin ligases-diversity supplementR35GM136250 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MICHELE PAGANO · 2020 to 2026
$2.7M
Chemical approaches for precision genome editingR01GM137606 · NIGMS · BROAD INSTITUTE, INC. · PI CHOUDHARY, AMIT · 2021 to 2024
$1.5M
Development of synthetic gene drives using small moleculesR01GM132825 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI AKBARI, OMAR SULTAN, CHOUDHARY, AMIT · 2019 to 2022
$1.4M
NIGMS NIH HHS R01 GM132825NIGMS NIH HHS R01 GM137606NIGMS NIH HHS R35 GM136250
6 · The paper itself

Abstract

Immunomodulatory drugs (IMiDs), which include thalidomide and its derivatives, have emerged as the standard of care against multiple myeloma. They function as molecular glues that bind to the E3 ligase cereblon (CRBN) and induce protein interactions with neosubstrates, including the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3). The subsequent ubiquitylation and degradation of these transcription factors underlies the antiproliferative activity of IMiDs. Here, we introduce photoswitchable immunomodulatory drugs (PHOIMiDs) that can be used to degrade Ikaros and Aiolos in a light-dependent fashion. Our lead compound shows minimal activity in the dark and becomes an active degrader upon irradiation with violet light. It shows high selectivity over other transcription factors, regardless of its state, and could therefore be used to control the levels of Ikaros and Aiolos with high spatiotemporal precision.

Indexed as

cancerimmunomodulatory drugs (IMiDs)molecular gluesphotopharmacologystructure-activity relationships

Identifiers

PMID37066279
PMCPMC10104231
OpenAlexW4362735629

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.