Evidence map›Paper›PMID 32753386›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

Synthetic nanobodies as angiotensin receptor blockers.

Conor McMahon, Dean P Staus, Laura M Wingler, Jialu Wang, Meredith A Skiba, Matthias Elgeti, Wayne L Hubbell, Howard A Rockman, Andrew C Kruse, Robert J Lefkowitz

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

42 citing papers in PubMed, 58 citations in OpenAlex.

  1. Review
  2. Activation of the angiotensin II type I receptor by a nonpeptide agonist.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Extracellular nanobody screening using conformationally stable GPCR variants.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Epitope-directed selection of GPCR nanobody ligands with evolvable function.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  17. Review
  18. Structural mechanism of CBNature communications · 2024
    Article
  19. Article
  20. Article
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

10 authors at 5 institutions in 1 country.

Conor McMahonDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.ORCID 0000-0001-9971-7869
Dean P StausHoward Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710.
Laura M WinglerHoward Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710.ORCID 0000-0002-3688-5088
Jialu WangDepartment of Medicine, Duke University Medical Center, Durham, NC 27710.
Meredith A SkibaDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.ORCID 0000-0003-4615-6775
Matthias ElgetiJules Stein Eye Institute, University of California, Los Angeles, CA 90095.ORCID 0000-0002-0550-4852
Wayne L HubbellJules Stein Eye Institute, University of California, Los Angeles, CA 90095.
Howard A RockmanDepartment of Medicine, Duke University Medical Center, Durham, NC 27710.
Andrew C KruseDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115; andrew_kruse@hms.harvard.edu lefko001@receptor-biol.duke.edu.ORCID 0000-0002-1467-1222
Robert J LefkowitzHoward Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710; andrew_kruse@hms.harvard.edu lefko001@receptor-biol.duke.edu.ORCID 0000-0003-1472-7545
Harvard University · USHoward Hughes Medical Institute · USUniversity of California, Los Angeles · USDuke Medical Center · USDuke University · US

Funding

Regulation of Beta-Adrenergic Receptor Signaling by S-NitrosylationP01HL075443 · NHLBI · DUKE UNIVERSITY · PI MAO, LAN · 2004 to 2019
$26.1M
Molecular Regulation of Cardiovascular 7 TM ReceptorsR01HL016037 · NHLBI · DUKE UNIVERSITY · PI ROBERT J LEFKOWITZ · 1985 to 2026
$14.5M
MECHANISMS OF MALADAPTATION IN HEART FAILURER01HL056687 · NHLBI · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI Howard A Rockman · 1996 to 2026
$12.3M
MOLECULAR BASIS OF MEMBRANE EXCITATIONR01EY005216 · NEI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HUBBELL, WAYNE L · 1985 to 2019
$9.8M
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
NEI NIH HHS R01 EY005216NHLBI NIH HHS P01 HL075443NHLBI NIH HHS R01 HL016037NHLBI NIH HHS R01 HL056687NICHD NIH HHS R21 HD101596NIH HHS DP5 OD021345
6 · The paper itself

Abstract

There is considerable interest in developing antibodies as functional modulators of G protein-coupled receptor (GPCR) signaling for both therapeutic and research applications. However, there are few antibody ligands targeting GPCRs outside of the chemokine receptor group. GPCRs are challenging targets for conventional antibody discovery methods, as many are highly conserved across species, are biochemically unstable upon purification, and possess deeply buried ligand-binding sites. Here, we describe a selection methodology to enrich for functionally modulatory antibodies using a yeast-displayed library of synthetic camelid antibody fragments called "nanobodies." Using this platform, we discovered multiple nanobodies that act as antagonists of the angiotensin II type 1 receptor (AT1R). Following angiotensin II infusion in mice, we found that an affinity matured nanobody antagonist has comparable antihypertensive activity to the angiotensin receptor blocker (ARB) losartan. The unique pharmacology and restricted biodistribution of nanobody antagonists may provide a path for treating hypertensive disorders when small-molecule drugs targeting the AT1R are contraindicated, for example, in pregnancy.

Indexed as

Angiotensin Receptor AntagonistsSingle-Domain AntibodiesAnimalsAntibody AffinityBlood PressureCell LineHumansMiceReceptors, AngiotensinAngiotensin Receptor AntagonistsReceptors, AngiotensinSingle-Domain AntibodiesangiotensinGPCRhypertensionligandnanobodies

Identifiers

PMID32753386
PMCPMC7443875
OpenAlexW3047014325

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.