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(A) Structures of the HMGCR inhibitors lovastatin (1) and simvastatin (2) together with their active forms (3 and 4). (B) Cocrystal structure of HMGCR catalytic domain complexed with simvastatin acid (4) (PDB: 1HW9). The conjugated site is indicated by a red arrow. (C) Structures of the E3 ligase ligands pomalidomide (5) and VH032 (6). (D) A general scheme for the design of HMGCR-targeting PROTAC probes.
