Evidence map›Paper›PMID 25991664›Full record

ReviewOncotarget2015

Polypharmacology of small molecules targeting the ubiquitin-proteasome and ubiquitin-like systems.

Ivano Amelio, Vivien Landré, Richard A Knight, Andrey Lisitsa, Gerry Melino, Alexey V Antonov

Open access · diamondAbstract readReview
In one paragraph

Review in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.2field-weighted citation impact, top 22% of its field
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

8 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
  2. Article
  3. Computer-aided design of multi-target ligands at AJournal of cheminformatics · 2017
    Article
  4. SUMO, a small, but powerful, regulator of double-strand break repair.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017
    Review
  5. Article
  6. Article
  7. Review
  8. Ubiquitin-Proteasome System in Neurodegenerative Disorders.Journal of drug metabolism & toxicology · 2015
    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

6 authors at 3 institutions in 3 countries.

Ivano AmelioMedical Research Council Toxicology Unit, Leicester, UK.
Vivien LandréMedical Research Council Toxicology Unit, Leicester, UK.
Richard A KnightMedical Research Council Toxicology Unit, Leicester, UK.
Andrey LisitsaInstitute of Biomedical Chemistry of The Russian Academy of Medical Sciences, Moscow, Russia.
Gerry MelinoMedical Research Council Toxicology Unit, Leicester, UK.
Alexey V AntonovMedical Research Council Toxicology Unit, Leicester, UK.
Medical Research Council · GBInstitute of Biomedical Chemistry · RUUniversity of Rome Tor Vergata · IT

Funding

Medical Research Council MC_U132670600
6 · The paper itself

Abstract

Targeting the ubiquitin-proteasome system (UPS) and ubiquitin-like signalling systems (UBL) has been considered a promising therapeutic strategy to treat cancer, neurodegenerative and immunological disorders. There have been multiple efforts recently to identify novel compounds that efficiently modulate the activities of different disease-specific components of the UPS-UBL. However, it is evident that polypharmacology (the ability to affect multiple independent protein targets) is a basic property of small molecules and even highly potent molecules would have a number of "off target" effects. Here we have explored publicly available high-throughput screening data covering a wide spectrum of currently accepted drug targets in order to understand polypharmacology of small molecules targeting different components of the UPS-UBL. We have demonstrated that molecules targeting a given UPS-UBL protein also have high odds to target a given off target spectrum. Moreover, the off target spectrum differs significantly between different components of UPS-UBL. This information can be utilized further in drug discovery efforts, to improve drug efficiency and to reduce the risk of potential side effects of the prospective drugs designed to target specific UPS-UBL components.

Indexed as

PolypharmacologyAnimalsCysteine EndopeptidasesDatabases, FactualDrug DesignHumansMiceNeoplasmsProteasome Endopeptidase ComplexProtein Interaction MappingSignal TransductionSUMO-1 ProteinUbiquitinUbiquitinationUbiquitin-Conjugating EnzymesUbiquitin ThiolesteraseCysteine EndopeptidasesProteasome Endopeptidase ComplexSENP6 protein, humanSUMO-1 ProteinSUMO1 protein, humanUBE2N protein, humanUbiquitinUbiquitin-Conjugating EnzymesUbiquitin ThiolesteraseUCHL5 protein, humanSUMOUBC13UBLUCH37UPS

Identifiers

PMID25991664
PMCPMC4496386
OpenAlexW1505933280

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.