ArticleMolecular and cellular biology2015
Pharmacological Induction of Human Fetal Globin Gene in Hydroxyurea-Resistant Primary Adult Erythroid Cells.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 38 citations in OpenAlex.
- Identification of small molecule agonists of fetal hemoglobin expression for the treatment of sickle cell disease.PloS one · 2024Article
- Synthesis of Difluoroarymethyl-Substituted Benzimidazo[2,1-ACS omega · 2023Article
- Visible-light-promoted decarboxylative radical cascade cyclization to acylated benzimidazo/indolo[2,1-RSC advances · 2022Article
- Modulating hemoglobin allostery for treatment of sickle cell disease: current progress and intellectual property.Expert opinion on therapeutic patents · 2022Review
- Genome-based therapeutic interventions for β-type hemoglobinopathies.Human genomics · 2021Review
- Epigenetic Reexpression of Hemoglobin F Using Reversible LSD1 Inhibitors: Potential Therapies for Sickle Cell Disease.ACS omega · 2020Article
- Nrf2 activation in myeloid cells and endothelial cells differentially mitigates sickle cell disease pathology in mice.Blood advances · 2019Article
- Family cord blood banking for sickle cell disease: a twenty-year experience in two dedicated public cord blood banks.Haematologica · 2017Article
- 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
- New insights into sickle cell disease: mechanisms and investigational therapies.Current opinion in hematology · 2016Review
- Gene Therapy of the β-Hemoglobinopathies by Lentiviral Transfer of the β(A(T87Q))-Globin Gene.Human gene therapy · 2016Article
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6 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Pharmacological induction of the fetal γ globin gene and the consequent formation of HbF (α2/γ2) in adult erythroid cells are one feasible therapeutic strategy for sickle cell disease (SCD) and severe β-thalassemias. Hydroxyurea (HU) is the current drug of choice for SCD, but serious side effects limit its clinical use. Moreover, 30 to 50% of patients are irresponsive to HU treatment. We have used high-throughput screening to identify benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one and its derivatives (compounds I to VI) as potent γ globin inducers. Of the compounds, I to V exert superior γ globin induction and have better therapeutic potential than HU, likely because of their activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway and modulation of expression levels and/or chromosome binding of γ globin gene regulators, including BCL11A, and chromatin structure over the γ globin promoter. Unlike sodium butyrate (NaB), the global levels of acetylated histones H3 and H4 are not changed by compound II treatment. Remarkably, compound II induces the γ globin gene in HU-resistant primary human adult erythroid cells, the p38 signaling pathway of which appears to be irresponsive to HU and NaB as well as compound II. This study provides a new framework for the development of new and superior compounds for treating SCD and severe β-thalassemias.
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