ArticlePloS one2014
A cell-based high-throughput screen for novel chemical inducers of fetal hemoglobin for treatment of hemoglobinopathies.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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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.
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.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Identification of small molecule agonists of fetal hemoglobin expression for the treatment of sickle cell disease.PloS one · 2024Article
- Discovery of small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Challenges with risk mitigation in academic drug discovery: finding the best solution.Expert opinion on drug discovery · 2019Article
- Early Probe and Drug Discovery in Academia: A Minireview.High-throughput · 2018Review
- Mouse Models of Erythropoiesis and Associated Diseases.Methods in molecular biology (Clifton, N.J.) · 2018Review
- Kinetic assay shows that increasing red cell volume could be a treatment for sickle cell disease.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Epigenetic assays for chemical biology and drug discovery.Clinical epigenetics · 2017Review
- O-Linked N-Acetylglucosamine (O-GlcNAc) Transferase and O-GlcNAcase Interact with Mi2β Protein at the Aγ-Globin Promoter.The Journal of biological chemistry · 2016Article
- Therapeutic fetal-globin inducers reduce transcriptional repression in hemoglobinopathy erythroid progenitors through distinct mechanisms.Blood cells, molecules & diseases · 2016Article
- Animal models of β-hemoglobinopathies: utility and limitations.Journal of blood medicine · 2016Review
- Development and characterization of K562 cell clones expressing BCL11A-XL: Decreased hemoglobin production with fetal hemoglobin inducers and its rescue with mithramycin.Experimental hematology · 2015Article
- Demystifying the secret mission of enhancers: linking distal regulatory elements to target genes.Critical reviews in biochemistry and molecular biology · 2015Review
- Article
- A Novel High-Content Immunofluorescence Assay as a Tool to Identify at the Single Cell Level γ-Globin Inducing Compounds.PloS one · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Decades of research have established that the most effective treatment for sickle cell disease (SCD) is increased fetal hemoglobin (HbF). Identification of a drug specific for inducing γ-globin expression in pediatric and adult patients, with minimal off-target effects, continues to be an elusive goal. One hurdle has been an assay amenable to a high-throughput screen (HTS) of chemicals that displays a robust γ-globin off-on switch to identify potential lead compounds. Assay systems developed in our labs to understand the mechanisms underlying the γ- to β-globin gene expression switch during development has allowed us to generate a cell-based assay that was adapted for a HTS of 121,035 compounds. Using chemical inducer of dimerization (CID)-dependent bone marrow cells (BMCs) derived from human γ-globin promoter-firefly luciferase β-globin promoter-Renilla luciferase β-globin yeast artificial chromosome (γ-luc β-luc β-YAC) transgenic mice, we were able to identify 232 lead chemical compounds that induced γ-globin 2-fold or higher, with minimal or no β-globin induction, minimal cytotoxicity and that did not directly influence the luciferase enzyme. Secondary assays in CID-dependent wild-type β-YAC BMCs and human primary erythroid progenitor cells confirmed the induction profiles of seven of the 232 hits that were cherry-picked for further analysis.
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What OpenQuestion holds
Registered trials
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.