Development of inhibitors of biliverdin reductase for toxic hyperbilirubinemia

National Center For Advancing Translational Sciences

Investigators

Abstract

During this period, we confirmed the hits from high-throughput screening (HTS) and virtual screening (VS) in two biochemical assays. A biophysical assay (microscale thermophoresis, MST) was developed to confirm the direct binding of hits with the target. We confirmed three chemotype from HTS and one compound from VS. We also perform a screen of DNA encoded library (DEL) using a CRO service from X-Chem. 24 hits from DEL library screening were synthesized and delivered to us. We found that &RT; 50% hits were binding to the hBVRA protein but only 6 of them had weak activity. Our chemists are working on the SAR of two chemotypes (one from HTS and one from DEL screening).