Evidence map›Paper›PMID 36908700›Full record

ArticleRSC chemical biology2023

Accessing three-branched high-affinity cereblon ligands for molecular glue and protein degrader design.

Robert Kuchta, Christopher Heim, Alexander Herrmann, Samuel Maiwald, Yuen Lam Dora Ng, Izidor Sosič, Tim Keuler, Jan Krönke, Michael Gütschow, Marcus D Hartmann and 1 more

Abstract read
In one paragraph

Article in RSC chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Beilstein journal of organic chemistry · 2023
    Article
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

11 authors.

Robert KuchtaPharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn An der Immenburg 4 Bonn D-53121 Germany c.steinebach@uni-bonn.de.
Christopher HeimMax Planck Institute for Biology Tübingen Tübingen D-72076 Germany marcus.hartmann@tuebingen.mpg.de.ORCID https://orcid.org/0000-0001-8711-8607
Alexander HerrmannMax Planck Institute for Biology Tübingen Tübingen D-72076 Germany marcus.hartmann@tuebingen.mpg.de.ORCID https://orcid.org/0000-0002-4241-942X
Samuel MaiwaldMax Planck Institute for Biology Tübingen Tübingen D-72076 Germany marcus.hartmann@tuebingen.mpg.de.ORCID https://orcid.org/0000-0002-7235-2748
Yuen Lam Dora NgCharité, Department of Internal Medicine with Focus on Hematology, Oncology and Tumor Immunology Berlin D-12203 Germany.
Izidor SosičFaculty of Pharmacy, University of Ljubljana Ljubljana SI-1000 Slovenia.ORCID https://orcid.org/0000-0002-3370-4587
Tim KeulerPharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn An der Immenburg 4 Bonn D-53121 Germany c.steinebach@uni-bonn.de.
Jan KrönkeCharité, Department of Internal Medicine with Focus on Hematology, Oncology and Tumor Immunology Berlin D-12203 Germany.
Michael GütschowPharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn An der Immenburg 4 Bonn D-53121 Germany c.steinebach@uni-bonn.de.ORCID https://orcid.org/0000-0002-9376-7897
Marcus D HartmannMax Planck Institute for Biology Tübingen Tübingen D-72076 Germany marcus.hartmann@tuebingen.mpg.de.ORCID https://orcid.org/0000-0001-6937-5677
Christian SteinebachPharmaceutical Institute, Pharmaceutical & Medicinal Chemistry, University of Bonn An der Immenburg 4 Bonn D-53121 Germany c.steinebach@uni-bonn.de.ORCID https://orcid.org/0000-0001-5638-1955

Funding

Degrading therapeutically important kinases using small moleculesR01CA218278 · NCI · STANFORD UNIVERSITY · PI Eric Sebastian Fischer, NATHANAEL Schiander GRAY · 2019 to 2026
$4.6M
The molecular basis of IMiD induced neo-substrate recruitment to the CRL4CRBN ubiquitin E3 ligase.R01CA214608 · NCI · DANA-FARBER CANCER INST · PI Eric Sebastian Fischer · 2017 to 2026
$4.0M
NCI NIH HHS R01 CA214608NCI NIH HHS R01 CA218278
6 · The paper itself

Abstract

The Petasis borono-Mannich reaction was employed for an alternative entry towards three-branched cereblon ligands. Such compounds are capabable of making multiple interactions with the protein surface and possess a suitable linker exit vector. The high-affinity ligands were used to assemble prototypic new molecular glues and proteolysis targeting chimeras (PROTACs) targeting BRD4 for degradation. Our results highlight the importance of multicomponent reactions (MCRs) in drug discovery and add new insights into the rapidly growing field of protein degraders.

Identifiers

PMID36908700
PMCPMC9994103

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.