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

J Med Chem. 2022 Feb 10;65(3):2548-2557. doi: 10.1021/acs.jmedchem.1c01664. Epub 2021 Dec 27.


Biliverdin IXβ 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 μM), 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 (ΔH, ΔS, and KD) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Crystallography, X-Ray
  • Drug Repositioning
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism*
  • Humans
  • Molecular Dynamics Simulation
  • Nuclear Magnetic Resonance, Biomolecular
  • Oxidoreductases Acting on CH-CH Group Donors / antagonists & inhibitors*
  • Oxidoreductases Acting on CH-CH Group Donors / chemistry
  • Oxidoreductases Acting on CH-CH Group Donors / metabolism
  • Protein Binding
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / metabolism*
  • Thermodynamics
  • United States
  • United States Food and Drug Administration


  • Enzyme Inhibitors
  • Small Molecule Libraries
  • Oxidoreductases Acting on CH-CH Group Donors
  • biliverdin reductase