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METHOD FOR TREATING A SUBJECT SUFFERING FROM CONDITIONS ASSOCIATED WITH AN EXTRACELLULAR ZINC SPHINGOMYELINASE

机译:治疗与细胞外锌鞘氨醇单酶相关的疾病的方法

摘要

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 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 ceramide in the sample from (a); (c) determining the amount of zinc sphingomyelinase activity in the sample based on 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.
机译:本发明提供了一种用于治疗患有与细胞外锌鞘磷脂酶活性有关的病症的受试者的方法,该方法包括向该受试者施用一定量的有效降低该受试者的细胞外锌鞘磷脂酶活性的锌鞘磷脂酶抑制剂,从而治疗该受试者。 。本发明还提供了确定化合物是否抑制涉及神经酰胺形成的细胞外鞘磷脂锌酶活性的方法,该方法包括:(a)在已知与这种锌活性有关的酸性pH条件下接触含有鞘磷脂锌酶的样品。鞘磷脂酶,具有:(i)鞘磷脂锌酶的底物,和(ii)被评估的化合物; (b)测量来自(a)的样品中的神经酰胺; (c)根据在步骤(b)中测定的神经酰胺浓度,确定样品中锌鞘磷脂酶活性的量; (d)将在步骤(c)中确定的鞘磷脂酶活性的量与在不存在该化合物的情况下确定的鞘磷脂酶的活性的量进行比较,以确定该化合物是否抑制锌鞘磷脂酶的活性。

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