Repositioning Food and Drug Administration-Approved Drugs for Inhibiting Biliverdin IXβ Reductase B as a Novel Thrombocytopenia Therapeutic Target

Biliverdin IX beta reductase B (BLVRB) has recently been proposed as a novel therapeutic target for thrombocytopenia through its reactive oxygen species (ROS)-associated mechanism. Thus, we aim at repurposing drugs as new inhibitors of BLVRB. Based on IC50 (<5 mu M), we have identified 20 compounds out of 1496 compounds from the Food and Drug Administration (FDA)-approved library and have clearly mapped their binding sites to the active site. Furthermore, we show the detailed BLVRB-binding modes and thermodynamic properties (Delta H, Delta S, and K-D) with nuclear magnetic resonance (NMR) and isothermal titration calorimetry together with complex structures of eight water-soluble compounds. We anticipate that the results will serve as a novel platform for further in-depth studies on BLVRB effects for related functions such as ROS accumulation and megakaryocyte differentiation, and ultimately treatments of platelet disorders.

Automated summary

This study focuses on Biliverdin IX beta reductase B (BLVRB) as a novel therapeutic target for thrombocytopenia, with the goal of repurposing drugs as new inhibitors of BLVRB. Through screening a library of FDA-approved compounds, 20 potential compounds were identified with high binding affinity to BLVRB's active site. The detailed binding modes, thermodynamic properties, and complex structures of water-soluble compounds provide a foundation for further research on the effects of BLVRB on ROS accumulation and megakaryocyte differentiation, potentially leading to new treatments for platelet disorders.