Evidence map›Paper›PMID 38730234›Full record

ArticleNature communications2024

Aptameric hirudins as selective and reversible EXosite-ACTive site (EXACT) inhibitors.

Haixiang Yu, Shekhar Kumar, James W Frederiksen, Vladimir N Kolyadko, George Pitoc, Juliana Layzer, Amy Yan, Rachel Rempel, Samuel Francis, Sriram Krishnaswamy and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
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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

11 authors.

Haixiang YuDepartment of Surgery, Duke University, Durham, NC, USA.
Shekhar KumarResearch Institute, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
James W FrederiksenDepartment of Surgery, Duke University, Durham, NC, USA.
Vladimir N KolyadkoResearch Institute, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-4008-2461
George PitocDepartment of Surgery, Duke University, Durham, NC, USA.
Juliana LayzerDepartment of Surgery, Duke University, Durham, NC, USA.
Amy YanDepartment of Surgery, Duke University, Durham, NC, USA.
Rachel RempelDepartment of Surgery, Duke University, Durham, NC, USA.
Samuel FrancisDepartment of Emergency Medicine, Duke University Hospital, Durham, NC, USA.ORCID http://orcid.org/0000-0003-3210-0789
Sriram KrishnaswamyResearch Institute, Children's Hospital of Philadelphia, Philadelphia, PA, USA. skrishna@pennmedicine.upenn.edu.
Bruce A SullengerDepartment of Surgery, Duke University, Durham, NC, USA. bruce.sullenger@duke.edu.

Funding

Translating Mechanistic Insights into Intrinsic Xase FunctionP01HL139420 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI BRUCE ALAN SULLENGER · 2018 to 2026
$22.4M
American Heart Association (American Heart Association, Inc.) 23POST1018721NHLBI NIH HHS P01 HL139420U.S. Department of Health & Human Services | National Institutes of Health (NIH) P01-HL139420
6 · The paper itself

Abstract

Potent and selective inhibition of the structurally homologous proteases of coagulation poses challenges for drug development. Hematophagous organisms frequently accomplish this by fashioning peptide inhibitors combining exosite and active site binding motifs. Inspired by this biological strategy, we create several EXACT inhibitors targeting thrombin and factor Xa de novo by linking EXosite-binding aptamers with small molecule ACTive site inhibitors. The aptamer component within the EXACT inhibitor (1) synergizes with and enhances the potency of small-molecule active site inhibitors by many hundred-fold (2) can redirect an active site inhibitor's selectivity towards a different protease, and (3) enable efficient reversal of inhibition by an antidote that disrupts bivalent binding. One EXACT inhibitor, HD22-7A-DAB, demonstrates extraordinary anticoagulation activity, exhibiting great potential as a potent, rapid onset anticoagulant to support cardiovascular surgeries. Using this generalizable molecular engineering strategy, selective, potent, and rapidly reversible EXACT inhibitors can be created against many enzymes through simple oligonucleotide conjugation for numerous research and therapeutic applications.

Indexed as

Aptamers, NucleotideCatalytic DomainHirudinsThrombinAnimalsAnticoagulantsBinding SitesBlood CoagulationFactor XaFactor Xa InhibitorsHumansAnticoagulantsAptamers, NucleotideFactor XaFactor Xa InhibitorsHirudinsThrombin

Identifiers

PMID38730234
PMCPMC11087511

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Registered trials

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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.