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Computational methods for designing potential inhibitors for activin type IIb (ActRIIB) receptor for treatment of anaemia

Jie Gao, Peng Zhang, Xiao-qin Zhang, Xue-feng Zhang, Guang-yao Wu

Anaemia is a clinical syndrome of blood characterized by decrease in the haemoglobin content in the red blood cells resulting in the marked reduction of the oxygen carrying capacity of the blood. Activins are one of the important types of the Transforming Growth Factor (TGF) protein superfamily. There are various cellular processes in vertebrates from fertilization to adulthood is regulated by the TGF-β superfamily. The heteromeric complexes consisting of type I and type II receptors belonging to the TGFsuperfamily are involved in various signalling processes. The Activin receptor type IIB (ActRIIB) is a transmembrane receptor involved in the negative regulation of red blood cells and skeletal muscle cells. Thus the inhibition of ActRIIB receptor protein results in increased growth of red blood cells and helps to recover anaemic conditions in healthy volunteers as well as in caner or anaemic patients. Molecular docking simulation based in-silico virtual screening technique is used in current experimental study for developing potent inhibitor molecules for activin receptor type IIB of humans for treatment of anaemia. Two compounds ZINC05386901 and ZINC18157167 shows promising results with potent inhibition of the Activin type-II receptor protein of human as well as good pharmacokinetic properties are observed without presence of any toxic effects.