Small-molecule inhibitor: TAPI-2

Name

History: The design of TAPI-2 was based on that of TAPI, with the replacement of a naphthyl group by t-butyl (Arribas et al. (1996)).
Peptidases inhibited: Inhibits adam 17 peptidase. Human meprin is also inhibited (Kruse &etal, 2004).

CID at PubChem: 10093303
Structure
Chemical/biochemical name: N-{D,L-[2-(hydroxyaminocarbonyl)-methyl]-4-methylpentanoyl}-L-3-(tert-butyl)-alanyl-L-alanine 2-aminoethyl amide
Formula weight: 416

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).