US Patent Application 20100068786 - METHODS AND COMPOSITIONS FOR REVERSING P-GLYCOPROTEIN MEDICATED DRUG RESISTANCE
InventorsUS Classes435/196, Acting on ester bond (3.1)435/325, ANIMAL CELL, PER SE (E.G., CELL LINES, ETC.); COMPOSITION THEREOF; PROCESS OF PROPAGATING, MAINTAINING OR PRESERVING AN ANIMAL CELL OR COMPOSITION THEREOF; PROCESS OF ISOLATING OR SEPARATING AN ANIMAL CELL OR COMPOSITION THEREOF; PROCESS OF PREPARING A COMPOSITION CONTAINING AN ANIMAL CELL; CULTURE MEDIA THEREFORE536/28.4, The N-hetero ring is a 1,3-diazine ring, including hydrogenated (e.g., pyrimidines, etc.)536/28.54, Alkyl, or substituted alkyl, bonded directly to the 5-position of the diazine ring (e.g., thymidine, 5-methyl uridine, etc.)546/74, Two of the cyclos share at least three ring members (e.g., morphinans, etc.)548/321.1, Benzene ring bonded directly to the diazole ring564/360Additional hydroxy, bonded directly to carbon, or ether oxygen attached directly or indirectly to the acyclic carbon or chain by acyclic nonionic bonding with no amino nitrogen between the additional hydroxy or ether oxygen and the aryl ring or ring system (H of -OH may be replaced by a substituted or unsubstitited ammonium ion or a Group IA or IIA light metal)Attorney, Agent or FirmInternational ClassesC12N 9/16C07H 19/06 C07D 221/28 C07D 233/02 C07D 215/42 Abstract textA method for inhibiting therapeutic drug resistance within a cell over-expressing a membrane protein is provided. The method comprises synthesizing a dimeric prodrug inhibitor of a monomeric therapeutic agent; administering the dimeric prodrug inhibitor to the membrane protein together with the monomeric therapeutic agent; and occupying at least one substrate binding site of the membrane protein with the synthesized dimeric prodrug to allow the monomeric therapeutic agent to accumulate within the cell. The dimeric prodrug inhibitor contains a crosslinking agent that is adapted to breakdown under reducing conditions within the cytosol of the cell to cause the dimeric prodrug to revert back to a form equivalent to the monomeric therapeutic agent. |
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