Evidence map›Paper›PMID 33057063›Full record

ArticleScientific reports2020

Long-acting antibody ligand mimetics for HER4-selective agonism.

Lu Shan, Kimberly M Cook, Nantaporn Haskins, Bilal Omar, Yu Jiang, Andrew Garcia, Adem Koksal, Vaheh Oganesyan, Kim Rosenthal, Herren Wu and 2 more

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

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.4field-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

0 citing papers in PubMed, 4 citations in OpenAlex.

No citing paper in PubMed yet.

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

12 authors at 1 institution in 1 country.

Lu ShanAntibody Discovery and Protein Engineering, AstraZeneca, Gaithersburg, USA. shan@dnli.com.
Kimberly M CookAntibody Discovery and Protein Engineering, AstraZeneca, Gaithersburg, USA.
Nantaporn HaskinsAntibody Discovery and Protein Engineering, AstraZeneca, Gaithersburg, USA.
Bilal OmarEarly Oncology, AstraZeneca, Gaithersburg, USA.
Yu JiangClinical Pharmacology and Safety Science, R&D, AstraZeneca, Gaithersburg, USA.
Andrew GarciaAntibody Discovery and Protein Engineering, AstraZeneca, Gaithersburg, USA.
Adem KoksalAntibody Discovery and Protein Engineering, AstraZeneca, Gaithersburg, USA.
Vaheh OganesyanAntibody Discovery and Protein Engineering, AstraZeneca, Gaithersburg, USA.
Kim RosenthalAntibody Discovery and Protein Engineering, AstraZeneca, Gaithersburg, USA.
Herren WuAntibody Discovery and Protein Engineering, AstraZeneca, Gaithersburg, USA.
William F Dall'AcquaAntibody Discovery and Protein Engineering, AstraZeneca, Gaithersburg, USA.
Melissa M DamschroderAntibody Discovery and Protein Engineering, AstraZeneca, Gaithersburg, USA. melissa.damschroder@AstraZeneca.com.
AstraZeneca (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neuregulin protein 1 (NRG1) is a large (> 60-amino-acid) natural peptide ligand for the ErbB protein family members HER3 and HER4. We developed an agonistic antibody modality, termed antibody ligand mimetics (ALM), by incorporating complex ligand agonists such as NRG1 into an antibody scaffold. We optimized the linker and ligand length to achieve native ligand activity in HEK293 cells and cardiomyocytes derived from induced pluripotent stem cells (iPSCs) and used a monomeric Fc-ligand fusion platform to steer the ligand specificity toward HER4-dominant agonism. With the help of selectivity engineering, these enhanced ALM molecules can provide an antibody scaffold with increased receptor specificity and the potential to greatly improve the pharmacokinetics, stability, and downstream developability profiles from the natural ligand approach. This ligand mimetic design and optimization approach can be expanded to apply to other cardiovascular disease targets and emerging therapeutic areas, providing differentiated drug molecules with increased specificity and extended half-life.

Indexed as

Antibodies, MonoclonalHEK293 CellsHumansInduced Pluripotent Stem CellsKineticsLigandsMyocytes, CardiacNeuregulin-1Protein BindingReceptor, ErbB-4Signal TransductionAntibodies, MonoclonalERBB4 protein, humanLigandsNeuregulin-1NRG1 protein, humanReceptor, ErbB-4

Identifiers

PMID33057063
PMCPMC7566517
OpenAlexW3092681435

What OpenQuestion holds

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LicenceCC BY
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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.