Evidence map›Paper›PMID 33341501›Full record

ArticleBioorganic & medicinal chemistry2021

Synthesis and evaluation of tiaprofenic acid-derived UCHL5 deubiquitinase inhibitors.

Harshani S Gurusingha Arachchige, Poornima D H Herath Mudiyanselage, Garrett C VanHecke, Kush Patel, Hassan A Cheaito, Q Ping Dou, Young-Hoon Ahn

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

Article in Bioorganic & medicinal chemistry, 2021. 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
0.3field-weighted citation impact, top 45% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

  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

7 authors at 2 institutions in 1 country.

Harshani S Gurusingha ArachchigeDepartment of Chemistry, Wayne State University, Detroit, MI, USA.
Poornima D H Herath MudiyanselageDepartment of Chemistry, Wayne State University, Detroit, MI, USA.
Garrett C VanHeckeDepartment of Chemistry, Wayne State University, Detroit, MI, USA.
Kush PatelBarbara Ann Karmanos Cancer Institute, Departments of Oncology, Pharmacology and Pathology, School of Medicine, Wayne State University, Detroit, MI, USA.
Hassan A CheaitoBarbara Ann Karmanos Cancer Institute, Departments of Oncology, Pharmacology and Pathology, School of Medicine, Wayne State University, Detroit, MI, USA.
Q Ping DouBarbara Ann Karmanos Cancer Institute, Departments of Oncology, Pharmacology and Pathology, School of Medicine, Wayne State University, Detroit, MI, USA.
Young-Hoon AhnDepartment of Chemistry, Wayne State University, Detroit, MI, USA. Electronic address: yahn@chem.wayne.edu.
Wayne State University · USThe Barbara Ann Karmanos Cancer Institute · US

Funding

Chemical Methods for Dissecting Protein Glutathionylation in SarcomereR01HL131740 · NHLBI · WAYNE STATE UNIVERSITY · PI AHN, YOUNG-HOON, BHAGWAT, ASHOK S · 2017 to 2021
$1.8M
NHLBI NIH HHS R01 HL131740
6 · The paper itself

Abstract

The ubiquitin-proteasome system (UPS) plays an important role in maintaining protein homeostasis by degrading intracellular proteins. In the proteasome, poly-ubiquitinated proteins are deubiquitinated by three deubiquitinases (DUBs) associated with 19S regulatory particle before degradation via 20S core particle. Ubiquitin carboxyl-terminal hydrolase L5 (UCHL5) is one of three proteasome-associated DUBs that control the fate of ubiquitinated substrates implicated in cancer survival and progression. In this study, we have performed virtual screening of an FDA approved drug library with UCHL5 and discovered tiaprofenic acid (TA) as a potential binder. With molecular docking analysis and in-vitro DUB assay, we have designed, synthesized, and evaluated a series of TA derivatives for inhibition of UCHL5 activity. We demonstrate that one TA derivative, TAB2, acts as an inhibitor of UCHL5.

Indexed as

Cell Line, TumorDose-Response Relationship, DrugEnzyme InhibitorsHumansMolecular Docking SimulationMolecular StructurePropionatesStructure-Activity RelationshipUbiquitin ThiolesteraseEnzyme InhibitorsPropionatestiaprofenic acidUbiquitin ThiolesteraseUCHL5 protein, humanDeubiquitinaseProteasomeTiaprofenic acidUCHL5 inhibitor

Identifiers

PMID33341501
PMCPMC7880549
OpenAlexW3111190953

What OpenQuestion holds

Textmetadata
LicenceTDM
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.