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Publication Abstract from PubMed

Biliverdin IXbeta 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 muM), 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 (DeltaH, DeltaS, 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.

Repositioning Food and Drug Administration-Approved Drugs for Inhibiting Biliverdin IXbeta Reductase B as a Novel Thrombocytopenia Therapeutic Target.,Kim M, Ha JH, Choi J, Kim BR, Gapsys V, Lee KO, Jee JG, Chakrabarti KS, de Groot BL, Griesinger C, Ryu KS, Lee D J Med Chem. 2021 Dec 27. doi: 10.1021/acs.jmedchem.1c01664. PMID:34957824^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.