With the recent elucidation of the structures of the catalytic portion of human HMGR enzyme complexed with six different statins by a series of crystallography studies, new possibilities have opened up for the rational design and optimization of even better HGMR inhibitors.
A new study using comparative molecular field analysis (CoMFA) to establish three-dimensional quantitative structure-activity relationship (3D QSAR), while searching for novel active pharmacophores as potentially potent HGMR inhibitors, was recently published. Using this novel technique researchers were able to screen for compounds with high screening scores. In addition to the conventional statin-like compounds with HMG-like moiety, eight additional compounds with completely different pharmacophore structure were found. This structure-based virtual screening procedure is considered promising for rational quest and optimization of potential novel HGMR inhibitors.