Patent ID: 7529628

Claim:
A method for identifying an agent for use as an inhibitor of tumor necrosis factor- alpha converting enzyme (TACE) comprising: (a) employing the atomic coordinates of Table 3 to generate a three dimensional model which defines the atomic coordinates of a TACE catalytic domain having Valine 353 substituted for Glycine in the full length enzyme (wherein said substitution is at position 139 of said SEQ ID NO: 8) complexed to a ligand; (b) utilizing the model from step (a) to determine the points of interaction between said ligand and TACE to generate a specific three-dimensional target; (c) employing said target from step (b) to design or select potential agents by performing rational drug design; (d) synthesizing and/or contacting the potential agent with a proteolytic polypeptide comprising the catalytic domain of TACE or an active fragment thereof; and (e) determining the catalytic activity of said proteolytic polypeptide in the TACE activity assay; wherein a potential agent is identified as an agent that inhibits TACE when there is a decrease in the activity of said proteolytic polypeptide in the presence of the agent relative to in its absence.