(S,S)-TAPI-1

TNF-α converting enzyme (TACE, also known as ADAM17) is a zinc metalloprotease that cleaves the membrane-bound precursor of TNF-α to give the mature soluble form of TNF-α.^1,2 It also mediates the proteolytic release of several other cell-surface proteins, including TNF-α receptors (TNFRs). TAPI-1, known in the earlier literature as just TAPI, is an inhibitor of TACE that inhibits the cleavage of TNF-α, TNFRI (p60), and TNFRII (p80) with IC₅₀ values ranging from 5-100 ?M.^1,3,4 It also blocks the shedding of other TACE-dependent proteins, including IL-6R and Klotho, and may inhibit metalloproteases other than TACE.^2,5,6 TAPI-1 differs from TAPI-0 , structurally, by the presence of an aminoethyl addition at the alanyl group, and is generally more stable in tissue culture and in vivo.

1.Mohler, K.M., Sleath, P.R., Fitzner, J.N., et al.Protection against a lethal dose of endotoxin by an inhibitor of tumour necrosis factor processingNature370(6486)218-220(1994) 2.Müllberg, J., Durie, F.H., Otten-Evans, C., et al.A metalloprotease inhibitor blocks shedding of the IL-6 receptor and the p60 TNF receptorJ. Immunol.155(11)5198-5205(1995) 3.Crowe, P.D., Walter, B.N., Mohler, K.M., et al.A metalloprotease inhibitor blocks shedding of the 80-kD TNF receptor and TNF processing in T lymphocytesJ. Exp. Med.181(3)1502-1210(1995) 4.Hooper, N.M., Karran, E.H., and Turner, A.J.Membrane protein secretasesBiochem. J.321(2)265-279(1997) 5.Chen, C.D., Podvin, S., Gillespie, E., et al.Insulin stimulates the cleavage and release of the extracellular domain of klotho by ADAM10 and ADAM17Proc. Natl. Acad. Sci. USA104(50)19796-19801(2007) 6.Yamamoto, K., Miyazaki, K., and Higashi, S.Pericellular proteolysis by matrix metalloproteinase-7 is differentially modulated by cholesterol sulfate, sulfatide, and cardiolipinFEBS J.281(15)3346-3356(2014)