Evidence map›Paper›PMID 34373558›Full record

ArticleScientific reports2021

A KLK4 proteinase substrate capture approach to antagonize PAR1.

Eitan Rabinovitch, Koishiro Mihara, Amiram Sananes, Marianna Zaretsky, Michael Heyne, Julia Shifman, Amir Aharoni, Morley D Hollenberg, Niv Papo

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

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.1field-weighted citation impact, top 52% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. 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

9 authors at 3 institutions in 2 countries.

Eitan RabinovitchAvram and Stella Goldstein-Goren Department of Biotechnology Engineering, National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, P.O.B. 653, 84105, Beer-Sheva, Israel.
Koishiro MiharaDepartment of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Amiram SananesAvram and Stella Goldstein-Goren Department of Biotechnology Engineering, National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, P.O.B. 653, 84105, Beer-Sheva, Israel.
Marianna ZaretskyDepartment of Life Sciences, National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Michael HeyneAvram and Stella Goldstein-Goren Department of Biotechnology Engineering, National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, P.O.B. 653, 84105, Beer-Sheva, Israel.
Julia ShifmanDepartment of Biological Chemistry, The Hebrew University of Jerusalem, Givat Ram Campus, 91906, Jerusalem, Israel.
Amir AharoniDepartment of Life Sciences, National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Morley D HollenbergDepartment of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Niv PapoAvram and Stella Goldstein-Goren Department of Biotechnology Engineering, National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, P.O.B. 653, 84105, Beer-Sheva, Israel. papo@bgu.ac.il.
Ben-Gurion University of the Negev · ILHebrew University of Jerusalem · ILUniversity of Calgary · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Proteinase-activated receptor-1 (PAR1), triggered by thrombin and other serine proteinases such as tissue kallikrein-4 (KLK4), is a key driver of inflammation, tumor invasiveness and tumor metastasis. The PAR1 transmembrane G-protein-coupled receptor therefore represents an attractive target for therapeutic inhibitors. We thus used a computational design to develop a new PAR1 antagonist, namely, a catalytically inactive human KLK4 that acts as a proteinase substrate-capture reagent, preventing receptor cleavage (and hence activation) by binding to and occluding the extracellular R41-S42 canonical PAR1 proteolytic activation site. On the basis of in silico site-saturation mutagenesis, we then generated KLK4

Indexed as

Platelet Aggregation InhibitorsAmino Acid SubstitutionBinding SitesCell Line, TumorComputer SimulationDrug DesignHumansKallikreinsKineticsMCF-7 CellsMutagenesis, Site-DirectedNeoplasm InvasivenessProtein EngineeringProtein Interaction Domains and MotifsProteolysisReceptor, PAR-1kallikrein 4KallikreinsPlatelet Aggregation InhibitorsReceptor, PAR-1Recombinant ProteinsThrombin

Identifiers

PMID34373558
PMCPMC8352894
OpenAlexW3188505039

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.