Figure 9.

Summary of preclinical efficacy and putative therapeutic target of bengamide-inspired analogues. (A) Structures of synthetic bengamides (i) (LAF389) explored in advance preclinical studies against HCT-116 tumor cells and (ii) LAF153 and LBM648 explored in target finding with MetAP1/MetAP2. (B) In silico docking of LAF389 with MetAP2. (C) X-ray cocrystal structure of LAF153 (a product of serum esterase action on LAF389) bound to hMetAP2, resolution 1.6 Å (adapted from J. Biol. Chem.2003, 278, 52964), which shows interaction of OR groups with several residues of the protein. Panels B and C are adapted from a lecture given by R. Versace, Novartis Pharmaceuticals, New Jersey, USA. Also compare these results to additional MetAP enzyme inhibition data in Table 3.