ArticleACS omega2025
Screen of the ReFRAME Compound Library for Therapeutic Agents to Prevent Red Blood Cell Sickling Using an Improved High Throughput Sickling Assay.
Article in ACS omega, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
10 authors.
Funding
Abstract
Sickle cell disease (SCD) is an autosomal recessive disorder of blood characterized by a mutation in the β chain of hemoglobin (Hb), leading to the production of sickle Hb (HbS). In SCD, under low oxygen conditions, red blood cells (RBCs) containing HbS form a characteristic "sickle" shape, resulting in chronic hemolytic anemia and acute vaso-occlusive crises. Current therapies for SCD have limitations in efficacy or availability, highlighting the need for new anti-sickling drugs. To facilitate the discovery of new anti-sickling compounds, we previously developed a high throughput sickling assay, which permits rapid screening of thousands of compounds for the ability to inhibit RBC sickling. In this study, we improved the sickling assay by optimizing the assay condition and expanded our screening efforts by evaluating the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) compound library, which contains approximately 2.5 times more compounds than previously screened. We were able to increase the number of blood samples that were adequate for identifying anti-sickling compounds in the improved sickling assay and identified voxelotor and SNS-314 as compounds that successfully prevented sickling. The improved sickling assay will increase access to valuable blood samples from SCD volunteers, providing more opportunities to develop anti-sickling compounds for treating SCD.
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Registered trials
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