Evidence map›Paper›PMID 29336885›Full record

ArticleStructure (London, England : 1993)2018

Structural Basis for Activity and Specificity of an Anticoagulant Anti-FXIa Monoclonal Antibody and a Reversal Agent.

Lauren K Ely, Marco Lolicato, Tovo David, Kate Lowe, Yun Cheol Kim, Dharmaraj Samuel, Paul Bessette, Jorge L Garcia, Thomas Mikita, Daniel L Minor and 1 more

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

Article in Structure (London, England : 1993), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 32% 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

5 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. 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

11 authors at 2 institutions in 1 country.

Lauren K ElyCenters for Therapeutic Innovation, San Francisco, Pfizer Inc., 1700 Owens Street, San Francisco, CA 94158, USA.
Marco LolicatoCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
Tovo DavidCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
Kate LoweCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
Yun Cheol KimCenters for Therapeutic Innovation, San Francisco, Pfizer Inc., 1700 Owens Street, San Francisco, CA 94158, USA.
Dharmaraj SamuelCenters for Therapeutic Innovation, San Francisco, Pfizer Inc., 1700 Owens Street, San Francisco, CA 94158, USA.
Paul BessetteCenters for Therapeutic Innovation, San Francisco, Pfizer Inc., 1700 Owens Street, San Francisco, CA 94158, USA.
Jorge L GarciaPMI PreClinical, 1031 Bing Street, San Carlos, CA 94070, USA.
Thomas MikitaCenters for Therapeutic Innovation, San Francisco, Pfizer Inc., 1700 Owens Street, San Francisco, CA 94158, USA. Electronic address: thomas.mikita@pfizer.com.
Daniel L MinorCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA; Molecular Biophysics and Integrated Bio-imaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: daniel.minor@ucsf.edu.
Shaun R CoughlinCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: shaun.coughlin@ucsf.edu.
Pfizer (United States) · USUniversity of California, San Francisco · US

Funding

Structure and function of voltage-gated calcium channelsR01HL080050 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DANIEL L MINOR · 2005 to 2026
$9.8M
NHLBI NIH HHS R01 HL080050
6 · The paper itself

Abstract

Coagulation factor XIa is a candidate target for anticoagulants that better separate antithrombotic efficacy from bleeding risk. We report a co-crystal structure of the FXIa protease domain with DEF, a human monoclonal antibody that blocks FXIa function and prevents thrombosis in animal models without detectable increased bleeding. The light chain of DEF occludes the FXIa S1 subsite and active site, while the heavy chain provides electrostatic interactions with the surface of FXIa. The structure accounts for the specificity of DEF for FXIa over its zymogen and related proteases, its active-site-dependent binding, and its ability to inhibit substrate cleavage. The inactive FXIa protease domain used to obtain the DEF-FXIa crystal structure reversed anticoagulant activity of DEF in plasma and in vivo and the activity of a small-molecule FXIa active-site inhibitor in vitro. DEF and this reversal agent for FXIa active-site inhibitors may help support clinical development of FXIa-targeting anticoagulants.

Indexed as

AnimalsAntibodies, MonoclonalAnticoagulantsBinding Sites, AntibodyFactor XIaHumansProtein ConformationThrombosisAntibodies, MonoclonalAnticoagulantsFactor XIaactive-site inhibitoranticoagulantcoagulationcrystal structurefactor XIhemostasisIgGintrinsic pathwayprotease-blocking antibodyprotease inhibitorthrombosis

Identifiers

PMID29336885
PMCPMC5803430
OpenAlexW2784171883

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.