Summary
Development of novel small molecule therapeutics for Sickle Cell Disease using an innovative imaging assay for high-throughput screening and subsequent in vivo testing.
Small Molecule Therapeutics for Sickle Cell Anemia
US · IL
NIH
grant
awarded
#nih-5R33HL163743-03
What they want
The R61 phase involves large-scale, high-throughput drug screening to identify molecules that prevent sickling of diseased red blood cells (RBCs). Resulting hits will be verified in dose response and secondary assays. Lead compounds will be selected based on physiologically acceptable changes of hemoglobin oxygen affinity and RBC membrane deformability. The R33 phase includes further optimization by medicinal chemistry, where lead scaffolds will be synthesized and evaluated for anti-sickling potency, hemoglobin oxygen affinity, and improved RBC membrane deformability. Townes HbSS mice will be used to test short term lethality, efficacy of anti-sickling activity, RBC oxygen affinity, and RBC half-life in vivo.
Deliverables
- Anti-sickling candidates for future pre-clinical and clinical studies
- 3 or more drug candidates that are safe and efficacious in the mouse model for future pre-clinical studies
Technical requirements
- Innovative imaging assay utilizing automated microscopy and customized algorithms
- Assay miniaturized to 1536-well plate format
- Townes HbSS mice expressing human globin genes for in vivo testing
