Evidence map›Paper›PMID 37662341›Full record

ArticlebioRxiv : the preprint server for biology2023

Antibodies Expand the Scope of Angiotensin Receptor Pharmacology.

Meredith A Skiba, Sarah M Sterling, Shaun Rawson, Morgan S A Gilman, Huixin Xu, Genevieve R Nemeth, Joseph D Hurley, Pengxiang Shen, Dean P Staus, Jihee Kim and 4 more

Open access · greenAbstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. 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
–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

0 citing papers in PubMed, 4 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 1 country.

Meredith A SkibaDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Sarah M SterlingDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Shaun RawsonDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Morgan S A GilmanDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Huixin XuDepartment of Pathology, Boston Children's Hospital, Boston, MA, 02115, USA.
Genevieve R NemethDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Joseph D HurleyDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Pengxiang ShenDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, 02138, USA.
Dean P StausDepartment of Medicine and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
Jihee KimDepartment of Medicine and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
Conor McMahonDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Maria K LehtinenDepartment of Pathology, Boston Children's Hospital, Boston, MA, 02115, USA.
Laura M WinglerDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.
Andrew C KruseDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Harvard University · USBoston Children's Hospital · USHoward Hughes Medical Institute · USDuke University · US

Funding

Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI Hisashi Umemori · 2021 to 2026
$9.4M
Making antibody generation rapid, scalable, and democratic through machine learning and continuous evolutionR01CA260415 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI KRUSE, ANDREW, LIU, CHANG C · 2020 to 2024
$8.4M
Control of neural stem cells by the nascent cerebrospinal fluidR01NS088566 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI LEHTINEN, MARIA · 2014 to 2024
$5.5M
Molecular mechanisms of adiponectin signaling and PAQR functionDP5OD021345 · OD · HARVARD MEDICAL SCHOOL · PI KRUSE, ANDREW · 2015 to 2019
$2.1M
Angiotensin receptor blocking antibody fragments as next-generation therapeutics for preeclampsiaR21HD101596 · NICHD · HARVARD MEDICAL SCHOOL · PI KRUSE, ANDREW · 2020 to 2021
$424k
NCI NIH HHS R01 CA260415NICHD NIH HHS P50 HD105351NICHD NIH HHS R21 HD101596NIH HHS DP5 OD021345NINDS NIH HHS R01 NS088566
6 · The paper itself

Abstract

G protein-coupled receptors (GPCRs) are key regulators of human physiology and are the targets of many small molecule research compounds and therapeutic drugs. While most of these ligands bind to their target GPCR with high affinity, selectivity is often limited at the receptor, tissue, and cellular level. Antibodies have the potential to address these limitations but their properties as GPCR ligands remain poorly characterized. Here, using protein engineering, pharmacological assays, and structural studies, we develop maternally selective heavy chain-only antibody ("nanobody") antagonists against the angiotensin II type I receptor (AT1R) and uncover the unusual molecular basis of their receptor antagonism. We further show that our nanobodies can simultaneously bind to AT1R with specific small-molecule antagonists and demonstrate that ligand selectivity can be readily tuned. Our work illustrates that antibody fragments can exhibit rich and

Identifiers

PMID37662341
PMCPMC10473732
OpenAlexW4386127004

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.