Since the early 1970's, several classes of natural products have been shown to inhibit the synthesis of β-1,3-glucan, an important polysaccharide component of the fungal cell wall.  The echinocandins, cyclic hexapeptides produced by certain Aspergillus species, were the first inhibitors to be identified.  Several other classes of lipopeptides, along with the papulacandins, and a variety of glycosidic terpenoid compounds have also been described as potent inhibitors of this enzyme.

The pneumocandins were first discovered at Merck Research Laboratories in the mid-1980's.  They are produced by Glarea lozoyensis and are structurally similar to the echinocandins, possessing several unusual amino acids and a dimethylmyristate side chain.  Modifications of the cyclic peptide nucleus resulted in improved potency and pharmacokinetic properties.  In general, introduction of cationic amine groups greatly improved these parameters and ultimately led to Cancidas^® (caspofungin acetate), the first β-1,3-glucan synthesis inhibitor indicated for the treatment of serious fungal infections.  The biology, SAR and clinical efficacy of this novel therapeutic agent will be discussed.