Modulation of drug resistance via ubiquitin carboxy-terminal hydrolase
AssigneeMillennium Pharmaceuticals, Inc.
InventorsAndrew W. Shyjan, Kyle J. MacBeth
Life of this patent
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Abstract
The expression of ubiquitin carboxy-terminal hydrolase is aberrent in cells that are resistant to treatment with chemical agents. Accordingly, the invention features methods for diagnosing and treating drug resistant cells (e.g., tumor cells) by examining and modulating the expression or activity of UCH.
Claims27
A method of determining whether a transformed mammalian cell will respond to a pharmaceutical agent, the method comprising
- (a) determining the level of activity of ubiquitin carboxy-terminal hydrolase in said transformed cell,
- (b) comparing the level of activity of ubiquitin carboxy-terminal hydrolase in said transformed cell with the level of activity of ubiquitin carboxy-terminal hydrolase in a nontransformed cell of the same type, and
- (c) identifying said transformed cell as being resistant to a pharmaceutical agent when there is an increased level of activity of ubiquitin carboxy-terminal hydrolase in said transformed cell compared to said nontransformed cell.
A method of identifying a compound that modulates drug resistance, the method comprising
- (a) determining the level of activity of ubiquitin carboxy-terminal hydrolase in a cell in the presence of a test compound,
- (b) comparing the level of activity of ubiquitin carboxy-terminal hydrolase in said cell in the presence and absence of said compound,
- (c) identifying said compound as a modulator of drug resistance when the level of ubiquitin carboxy-terminal hydrolase activity is decreased in the presence of said compound.
A method of identifying a compound that modulates drug resistance, the method comprising
- (a) determining the level of expression of ubiquitin carboxy-terminal hydrolase in a cell in the presence of a selected compound,
- (b) comparing the level of expression of ubiquitin carboxy-terminal hydrolase in said cell in the presence and absence of said selected compound.
- (c) identifying said compound as a modulator of drug resistance when the level of ubiquitin carboxy-terminal hydrolase activity is decreased in the presence of said compound.
A method of identifying a compound that modulates drug resistance, the method comprising
- (a) determining whether a selected compound specifically binds ubiquitin carboxy-terminal hydrolase, and
- (b) identifying said selected compound as a modulator of drug resistance if said compound selectively binds ubiquitin carboxy-terminal hydrolase.
Dependencies are inferred from the claim text.