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Inhibitor of ceramidase
| Details |
Inventors: Hannun, Yusuf A.; Bielawska, Alicja; McKay, Charles;
Assignee: Duke University (Durham, NC)
Primary Examiner: Raymond; Richard L.
Assistant Examiner:
Attorney, Agent or Firm: Nixon & Vanderhye P.C.
The present invention relates, in general, to the bioeffector molecule ceramide and, in particular, to methods of effecting intracellular accumulation of ceramide. The invention further relates to methods of selecting compounds that inhibit alkaline ceramidase and that can be used to treat diseases/disorders associated with cell hyperplasia or dedifferentiation. |
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DETAILED DESCRIPTION It is a general object of the invention to provide a method of selecting compounds that cause intracellular accumulation of ceramide.
It is a specific object of the invention to provide a method of identifying compounds that can be used to effect the selective inhibition of alkaline ceramidase.
It is a further object of the invention to provide a method of selecting compounds that can be used to treat hyperproliferative diseases/disorders.
The foregoing objects are met by the present invention.
In one embodiment, the present invention relates to a method of increasing intracellular levels of ceramide in a mammal.
The method comprises administering to the mammal an agent that inhibits alkaline ceramidase in an amount sufficient to effect the inhibition, and monitoring the intracellular levels of ceramide.
In a further embodiment, the present invention relates to a method of treating a disease or disorder associated with cell hyperplasia.
The method comprises administering to a mammal in need of such treatment an agent that inhibits alkaline ceramidase in an amount sufficient to effect the inhibition, and monitoring intracellular levels of ceramide in the mammal.
In yet another embodiment, the present invention relates to a method of testing a compound for its ability to inhibit mammalian alkaline ceramidase.
The method comprises i) contacting the compound with a sample comprising mammalian alkaline ceramidase, in the presence of ceramide, under conditions such that the alkaline ceramidase degrades ceramide to sphingosine in the absence of the compound, and ii) determining the level of degradation of ceramide resulting from step (i) and comparing that level to a level of degradation obtained in the absence of the compound.
Further objects and advantages of the invention will be clear from the description that follows.
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