Evidence map›Paper›PMID 30528168›Full record

ArticleBioorganic & medicinal chemistry letters2019

Diarylcarbonates are a new class of deubiquitinating enzyme inhibitor.

Marcus J C Long, Ann P Lawson, Rick Baggio, Yu Qian, Lior Rozhansky, Domenico Fasci, Farid El Oualid, Eranthie Weerapana, Lizbeth Hedstrom

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Review
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

9 authors.

Marcus J C LongGraduate Program in Biochemistry and Biophysics Brandeis University, 415 South Street, Waltham, MA 02453, USA.
Ann P LawsonDepartment of Biology, Brandeis University, 415 South Street, Waltham, MA 02453, USA.
Rick BaggioGraduate Program in Biochemistry and Biophysics Brandeis University, 415 South Street, Waltham, MA 02453, USA.
Yu QianDepartment of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467, USA.
Lior RozhanskyDepartment of Biology, Brandeis University, 415 South Street, Waltham, MA 02453, USA.
Domenico FasciSanford-Burnham Medical Research Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Farid El OualidUbiQ Bio BV, Science Park 408, 1098 XH Amsterdam, the Netherlands.
Eranthie WeerapanaDepartment of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467, USA.
Lizbeth HedstromDepartment of Biology, Brandeis University, 415 South Street, Waltham, MA 02453, USA; Department of Chemistry(3), Brandeis University, 415 South Street, Waltham, MA 02453, USA. Electronic address: hedstrom@brandeis.edu.

Funding

Investigating cysteine-mediated protein activities in C. elegansR01GM118431 · NIGMS · BOSTON COLLEGE · PI WEERAPANA, ERANTHIE · 2015 to 2019
$1.8M
Inhibitor mediated protein degradationR01GM100921 · NIGMS · BRANDEIS UNIVERSITY · PI HEDSTROM, LIZBETH K. · 2012 to 2015
$1.2M
Howard Hughes Medical InstituteNIGMS NIH HHS R01 GM100921NIGMS NIH HHS R01 GM118431
6 · The paper itself

Abstract

Promiscuous inhibitors of tyrosine protein kinases, proteases and phosphatases are useful reagents for probing regulatory pathways and stabilizing lysates as well as starting points for the design of more selective agents. Ubiquitination regulates many critical cellular processes, and promiscuous inhibitors of deubiquitinases (DUBs) would be similarly valuable. The currently available promiscuous DUB inhibitors are highly reactive electrophilic compounds that can crosslink proteins. Herein we introduce diarylcarbonate esters as a novel class of promiscuous DUB inhibitors that do not have the liabilities associated with the previously reported compounds. Diarylcarbonates stabilize the high molecular weight ubiquitin pools in cells and lysates. They also elicit cellular phenotypes associated with DUB inhibition, demonstrating their utility in ubiquitin discovery. Diarylcarbonates may also be a useful scaffold for the development of specific DUB inhibitors.

Indexed as

CarbonatesDeubiquitinating EnzymesDose-Response Relationship, DrugEnzyme InhibitorsHumansMolecular StructureStructure-Activity RelationshipUbiquitinationCarbonatesDeubiquitinating EnzymesEnzyme InhibitorsActivity profilingBcr AblMdm2USP7USP9

Identifiers

PMID30528168
PMCPMC6467287

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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.