Small-molecule inhibitor: matlystatin B

Name

History: Matlystatin B was one of five matlystatins discovered as products of Actinomadura atramentaria by Ogita et al. (1992).
Peptidases inhibited: Inhibits matrix metallopeptidase-2 and matrix metallopeptidase-9 (Tanzawa et al., 1992).
Mechanism: Inhibition is reversible.

CID at PubChem: 132321
Structure
Chemical/biochemical name: 2-[2-(carbamoylmethyl)heptanoyl]-1-hydroxy-N-(3-methyl-5-oxo-heptan-4-yl)diazinane-3-carboxamide
Formula weight: 441
Related inhibitors: R-94138 (analogue from Actinomadura atramentaria: Matsuoka et al., 2000); matlystatins A, D, E, F.

Inhibitor class: This compound contains functionality of the hydroxamate class of metallopeptidase inhibitors. The first full report of hydroxamates as metallopeptidase inhibitors was that of Nishino & Powers (1978). These are reversible inhibitors in which the hydroxamic acid group forms a bidentate complex with the active site zinc. A structure (Holmes & Matthews, 1981) showed both the carbonyl oxygen and the hydroxyl oxygen close to the zinc. Specificity is achieved by fitting of other parts of the molecules to prime-side substrate-binding sites. An excellent early review of the hydroxamates as metallopeptidase inhibitors was that of Powers & Harper (1986) (pp. 244-253).
Comment: The IC₅₀ of a synthetic analogue of matlystatin B was 475-fold lower than that of matlystatin B itself towards matrix metallopeptidase-9 (Tamaki et al., 1995).