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1. (WO1999011283) METHOD FOR TREATING A SUBJECT SUFFERING FROM CONDITIONS ASSOCIATED WITH AN EXTRACELLULAR ZINC SPHINGOMYELINASE

Pub. No.:    WO/1999/011283    International Application No.:    PCT/US1998/018362
Publication Date: Mar 11, 1999 International Filing Date: Sep 4, 1998
IPC: A61K 38/00
A61K 38/46
C07K 16/40
Applicants: THE TRUSTEES OF COLOMBIA UNIVERSITY IN THE CITY OF NEW YORK
TABAS, Ira
SCHISSEL, Scott, L.
WILLIAMS, Kevin, Jon
Inventors: TABAS, Ira
SCHISSEL, Scott, L.
WILLIAMS, Kevin, Jon
Title: METHOD FOR TREATING A SUBJECT SUFFERING FROM CONDITIONS ASSOCIATED WITH AN EXTRACELLULAR ZINC SPHINGOMYELINASE
Abstract:
The present invention provides for a method for treating a subject suffering from a condition associated with an extracellular zinc sphingomyelinase activity which comprises administering to the subject an amount of a zinc sphingomyelinase inhibitor effective to decrease extracellular zinc sphingomyelinase activity in the subject and thereby treat the subject. The present invention also provides for a method for determining whether a compound inhibits an activity of an extracellular zinc sphingomyelinase involving ceramide formation which comprises: (a) contacting a sample containing the zinc sphingomyelinase under acidic pH conditions known to be associated with the activity of such zinc sphingomyelinase, with: (i) a substrate of the zinc sphingomyelinase enzyme, and (ii) the compound being evaluated; (b) measuring the concentration of ceramide in the sample from (a); (c) determining the amount of zinc sphingomyelinase activity in the sample based upon the concentration of ceramide measured in step (b); and (d) comparing the amount of sphingomyelinase activity determined in step (c) with the amount of sphingomyelinase activity determined in the absence of the compound, so as to determine whether the compound inhibits the activity of zinc sphingomyelinase.