Evidence map›Paper›PMID 35729701›Full record

ArticleAnalytical chemistry2022

On-Chip Preconcentration Microchip Capillary Electrophoresis Based CE-PRM-LIVE for High-Throughput Selectivity Profiling of Deubiquitinase Inhibitors.

He Zhu, J Scott Mellors, Wai Cheung Chan, J Will Thompson, Scott B Ficarro, Isidoro Tavares, Ariana S Bratt, Jens Decker, Michael Krause, Gary Kruppa and 2 more

Abstract read
In one paragraph

Article in Analytical chemistry, 2022. 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. Article
  2. 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

12 authors.

He ZhuDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, United States.ORCID 0000-0002-9925-2640
J Scott Mellors908 Devices Inc., Boston, Massachusetts 02210, United States.ORCID 0000-0002-6658-3961
Wai Cheung ChanDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, United States.ORCID 0000-0001-8413-5401
J Will Thompson908 Devices Inc., Boston, Massachusetts 02210, United States.ORCID 0000-0001-6567-1268
Scott B FicarroDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, United States.
Isidoro TavaresDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, United States.
Ariana S BrattDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, United States.
Jens DeckerBruker Daltonics GmbH & Co. KG, Bremen 28359, Germany.
Michael KrauseBruker Daltonics GmbH & Co. KG, Bremen 28359, Germany.
Gary KruppaBruker S.R.O., District Brno-City 61900 Czech Republic.
Sara J BuhrlageDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, United States.ORCID 0000-0003-4562-1823
Jarrod A MartoDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, United States.ORCID 0000-0003-2086-1134

Funding

Illuminating Function of the Understudied Druggable KinomeU24DK116204 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JOHNSON, GARY L. · 2017 to 2022
$13.6M
Novel Screening Platform for Discovery of DUB Targeting ProbesR01CA233800 · NCI · DANA-FARBER CANCER INST · PI BUHRLAGE, SARA J, MARTO, JARROD A. · 2019 to 2022
$2.5M
Tools for DUB Drug DiscoveryR21CA247671 · NCI · DANA-FARBER CANCER INST · PI BUHRLAGE, SARA J, MARTO, JARROD A. · 2020 to 2021
$648k
NCI NIH HHS R01 CA233800NCI NIH HHS R21 CA247671NIDDK NIH HHS U24 DK116204
6 · The paper itself

Abstract

The family of deubiquitinases (DUBs) comprises ∼100 enzymes that cleave ubiquitin from substrate proteins and thereby regulate key aspects of human physiology. DUBs have recently emerged as disease-relevant and chemically tractable, although currently there are no approved DUB-targeting drugs and most preclinical small molecules are low-potency and/or multitargeted. We paired a novel capillary electrophoresis microchip containing an integrated, "on-chip" C18 bed (SPE-ZipChip) with a TMT version of our recently described PRM-LIVE acquisition scheme on a timsTOF Pro mass spectrometer to facilitate rapid activity-based protein profiling of DUB inhibitors. We demonstrate the ability of the SPE-ZipChip to improve proteome coverage of complex samples as well as the quantitation integrity of CE-PRM-LIVE for TMT labeled samples. These technologies provide a platform to accurately quantify competitive binding of covalent and reversible inhibitors in a multiplexed assay that spans 49 endogenous DUBs in less than 15 min.

Indexed as

Electrophoresis, MicrochipUbiquitinDeubiquitinating EnzymesElectrophoresis, CapillaryHumansProteomeDeubiquitinating EnzymesProteomeUbiquitin

Identifiers

PMID35729701
PMCPMC10654755

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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.