Small-molecule inhibitor: elasnin

Name

History: Elasnin was discovered as a natural product of Streptomyces noboritoensis (Omura et al., 1978; Ohno et al., 1978).
Peptidases inhibited: Neutrophil elastase (IC₅₀ = 3.3 x10^-6 M), pancreatic elastase (IC₅₀ = 77 x10^-6 M), chymotrypsin (weakly).
Mechanism: Elasnin is an alkyl-substituted, 2-hydroxy-4-pyrone; it is highly lipophilic, and may interact with the same hydrophobic binding site in neutrophil elastase as fatty acids such as oleic acid (K_i = 9 x10^-6 M: Powers & Harper, 1986). Inhibition is fully reversible, there being no evidence of enzyme acylation by the pyrone (Spencer et al., 1985). The extent of competition with substrate was variable in a series of analogues of elasnin (Cook et al., 1987).
Pharmaceutical relevance: Inhibitors of leukocyte elastase are of interest as possible therapeutic agents for chronic obstructive lung diseases, but elasnin itself is probably not potent enough to be useful. Sets of synthetic analogues have been produced and evaluated by Spencer et al. (1985), Groutas et al. (1985) and Cook et al. (1987).

CID at PubChem: 129277
Structure
Chemical/biochemical name: 3,5-dibutyl-2-hydroxy-6-(6-oxoundecan-5-yl)pyran-4-one
Formula weight: 393