Evidence map›Paper›PMID 31147439›Full record

ArticleHaematologica2020

A novel, highly potent and selective phosphodiesterase-9 inhibitor for the treatment of sickle cell disease.

James G McArthur, Niels Svenstrup, Chunsheng Chen, Aurelie Fricot, Caroline Carvalho, Julia Nguyen, Phong Nguyen, Anna Parachikova, Fuad Abdulla, Gregory M Vercellotti and 5 more

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

Article in Haematologica, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
4.8field-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

27 citing papers in PubMed, 51 citations in OpenAlex.

  1. Trial
  2. Observational
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  8. Article
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  10. Article
  11. Advancing the care of β-thalassaemia patients with novel therapies.Blood transfusion = Trasfusione del sangue · 2022
    Review
  12. β-Thalassemia: evolving treatment options beyond transfusion and iron chelation.Hematology. American Society of Hematology. Education Program · 2021
    Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. Sickle cell vaso-occlusion: The dialectic between red cells and white cells.Experimental biology and medicine (Maywood, N.J.) · 2021
    Review
  19. Review
  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

15 authors at 7 institutions in 3 countries.

James G McArthurImara Inc., 2 Floor, 700 Technology Square, Cambridge, MA, USAImara Inc., 2 jmcarthur@cydanco.com.
Niels SvenstrupH. Lundbeck A/S, Ottiliavej 9, 2500 Valby, Denmark.
Chunsheng ChenDepartment of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.
Aurelie FricotINSERM UMR 1163, CNRS ERL 8254, Imagine Institute, Laboratory of Excellence GR-Ex, Paris Descartes - Sorbonne Paris Cité University, Paris, France.
Caroline CarvalhoINSERM UMR 1163, CNRS ERL 8254, Imagine Institute, Laboratory of Excellence GR-Ex, Paris Descartes - Sorbonne Paris Cité University, Paris, France.
Julia NguyenDepartment of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.
Phong NguyenDepartment of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.
Anna ParachikovaH. Lundbeck A/S, Ottiliavej 9, 2500 Valby, Denmark.
Fuad AbdullaDepartment of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.
Gregory M VercellottiDepartment of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.
Olivier HermineINSERM UMR 1163, CNRS ERL 8254, Imagine Institute, Laboratory of Excellence GR-Ex, Paris Descartes - Sorbonne Paris Cité University, Paris, France.
Dave EdwardsKinexum, 8830 Glen Ferry Drive, Johns Creek, GA, USA.
Jean-Antoine RibeilDepartments of Biotherapy, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris Descartes- Sorbonne Paris Cité University, Paris, France.
John D BelcherDepartment of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.
Thiago T MacielINSERM UMR 1163, CNRS ERL 8254, Imagine Institute, Laboratory of Excellence GR-Ex, Paris Descartes - Sorbonne Paris Cité University, Paris, France.
University of Minnesota · USLundbeck (Denmark) · DKAssistance Publique – Hôpitaux de Paris · FRCentre National de la Recherche Scientifique · FRInstitut des Maladies Génétiques Imagine · FRLaboratory of Excellence GR-Ex · FRSorbonne Paris Cité · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The most common treatment for patients with sickle cell disease (SCD) is the chemotherapeutic hydroxyurea, a therapy with pleiotropic effects, including increasing fetal hemoglobin (HbF) in red blood cells and reducing adhesion of white blood cells to the vascular endothelium. Hydroxyurea has been proposed to mediate these effects through a mechanism of increasing cellular cGMP levels. An alternative path to increasing cGMP levels in these cells is through the use of phosphodiesterase-9 inhibitors that selectively inhibit cGMP hydrolysis and increase cellular cGMP levels. We have developed a novel, potent and selective phosphodiesterase-9 inhibitor (IMR-687) specifically for the treatment of SCD. IMR-687 increased cGMP and HbF in erythroid K562 and UT-7 cells and increased the percentage of HbF positive erythroid cells generated

Indexed as

Anemia, Sickle CellAnimalsFetal HemoglobinHumansHydroxyureaK562 CellsMicePhosphodiesterase InhibitorsPhosphoric Diester HydrolasesFetal HemoglobinHydroxyureaPhosphodiesterase InhibitorsPhosphoric Diester Hydrolases

Identifiers

PMID31147439
PMCPMC7049346
OpenAlexW2947033846

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.