ArticleProceedings of the National Academy of Sciences of the United States of America2022
Phenotypic screening of the ReFRAME drug repurposing library to discover new drugs for treating sickle cell disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Functional and multi-omics signatures of mitapivat efficacy upon activation of pyruvate kinase in red blood cells from patients with sickle cell disease.Haematologica · 2024Trial
- In vivo measurement of RBC survival in patients with sickle cell disease before or after hematopoietic stem cell transplantation.Blood advances · 2024Trial
- An AI-enabled tool for quantifying overlapping red blood cell sickling dynamics in microfluidic assays.Lab on a chip · 2026Article
- Mixing Is Dispensable for Optical Density-Based High-Throughput Growth Screening Assay in Fission Yeast.International journal of molecular sciences · 2026Article
- Pyruvate kinase deficiency modifies sickle hemoglobin carrier and sickle cell disease phenotypes in mice.JCI insight · 2026Article
- In Silico Post-screening of Anti-polymerization Agents to Treat Sickle Cell Disease.bioRxiv : the preprint server for biology · 2025Article
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- Genomics-driven drug repurposing and novel targets identification for sickle cell disease in Saudi patients.Frontiers in bioinformatics · 2025Article
- Therapeutic potential of the latest oxygen affinity-modifying agent, GBT021601, for treating sickle cell disease is questionable.British journal of haematology · 2024Article
- Sickle Cell Hemoglobin "Drugged" with Cyclic Peptides Is Aggregation Incompetent.The journal of physical chemistry. B · 2024Article
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- Development of pathophysiologically relevant models of sickle cell disease and β-thalassemia for therapeutic studies.Nature communications · 2024Article
- A framework of computer vision-enhanced microfluidic approach for automated assessment of the transient sickling kinetics in sickle red blood cells.Frontiers in physics · 2024Article
- Mocetinostat activates Krüppel-like factor 4 and protects against tissue destruction and inflammation in osteoarthritis.JCI insight · 2023Article
- Voxelotor does not inhibit sickle hemoglobin fiber formation upon complete deoxygenation.Biophysical journal · 2023Article
- Screen "play" for drug discovery.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Drug discovery by a basic research scientist.Frontiers in molecular biosciences · 2022Article
Corrections and comments
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- Erratum issued
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stem cell transplantation and genetic therapies offer potential cures for patients with sickle cell disease (SCD), but these options require advanced medical facilities and are expensive. Consequently, these treatments will not be available for many years to the majority of patients suffering from this disease. What is urgently needed now is an inexpensive oral drug in addition to hydroxyurea, the only drug approved by the FDA that inhibits sickle-hemoglobin polymerization. Here, we report the results of the first phase of our phenotypic screen of the 12,657 compounds of the Scripps ReFRAME drug repurposing library using a recently developed high-throughput assay to measure sickling times following deoxygenation to 0% oxygen of red cells from sickle trait individuals. The ReFRAME library is a very important collection because the compounds are either FDA-approved drugs or have been tested in clinical trials. From dose-response measurements, 106 of the 12,657 compounds exhibit statistically significant antisickling at concentrations ranging from 31 nM to 10 μM. Compounds that inhibit sickling of trait cells are also effective with SCD cells. As many as 21 of the 106 antisickling compounds emerge as potential drugs. This estimate is based on a comparison of inhibitory concentrations with free concentrations of oral drugs in human serum. Moreover, the expected therapeutic potential for each level of inhibition can be predicted from measurements of sickling times for cells from individuals with sickle syndromes of varying severity. Our results should motivate others to develop one or more of these 106 compounds into drugs for treating SCD.
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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.