Platensimycin (PTM, 1)1, 2 and platencin (PTN, 2)3, 4 are recently discovered natural products, which are potent and selective inhibitors of bacterial and mammalian fatty acid synthases (Figure 1a). They have emerged as promising drug leads for both antibacterial and antidiabetic therapies. Although the efficacy of PTM and PTN has been demonstrated in mouse models, they suffer from poor pharmacokinetic properties, mainly a high rate of clearance, thereby requiring continuous infusion to ensure adequate exposure, a delivery method that is not desirable to most patients. Consequently, significant effort has been undertaken to prepare PTM and PTN analogues by organic synthesis,8, 9 and to isolate PTM and PTN congeners by fermentation optimization. Although these analogues have helped define the structure–activity relationship of PTM and PTN, none of them however can be argued to have significantly improved therapeutic properties.
- Fatty acid synthase inhibitor
- Pathway regulation