Evidence map›Paper›PMID 16973749›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2006

A rationally designed agonist antibody fragment that functionally mimics thrombopoietin.

Shana Frederickson, Mark W Renshaw, Bing Lin, Lynette M Smith, Peter Calveley, Jeremy P Springhorn, Krista Johnson, Yi Wang, Xiao Su, Yamin Shen and 1 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
5.7field-weighted citation impact, top 4% 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

14 citing papers in PubMed, 52 citations in OpenAlex.

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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 at 1 institution in 1 country.

Shana FredericksonAlexion Antibody Technologies, Inc., 3985-A Sorrento Valley Boulevard, San Diego, CA 92121, USA.
Mark W Renshaw
Bing Lin
Lynette M Smith
Peter Calveley
Jeremy P Springhorn
Krista Johnson
Yi Wang
Xiao Su
Yamin Shen
Katherine S Bowdish
Alexion Pharmaceuticals (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

By using rational design, antibody fragments (Fabs) that mimic thrombopoietin (TPO) were created. A peptide with cMpl receptor-binding capability was grafted into different complementarity-determining regions of a fully human Fab scaffold. Functional presentation of the peptide was optimized by using phage display and cell-based panning. Select antibodies and fragments containing two grafted peptides were assayed for their ability to stimulate the cMpl receptor in vitro. Several candidates demonstrated agonist activity in an in vitro cMpl receptor signaling reporter assay, including Fab59, which was estimated to be equipotent to TPO. Fab59 additionally was able to effectively stimulate platelet production in normal mice. These rationally designed mimetic Fabs may provide a therapeutic intervention for thrombocytopenia while avoiding the potential generation of neutralizing antibodies to endogenous TPO. Furthermore, this study demonstrates a method by which short-lived linear peptides with binding activity may be converted to more stable and potent agonists capable of activating cell surface receptors.

Indexed as

Molecular MimicryAnimalsBlood PlateletsCells, CulturedCross-Linking ReagentsHumansImmunoglobulin Fab FragmentsMaleMiceMice, Inbred BALB CMolecular Sequence DataNIH 3T3 CellsPeptidesReceptors, Cell SurfaceSolubilityStructure-Activity RelationshipCross-Linking ReagentsImmunoglobulin Fab FragmentsPeptidesReceptors, Cell SurfaceThrombopoietin

Identifiers

PMID16973749
PMCPMC1599960
OpenAlexW1966662450

What OpenQuestion holds

Textmetadata
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.