Therapy of tumors and infectious agents deficient in methylthioadenosine phosphorylase
OwnerAdam Lubin, Martin Lubininventors
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Abstract
Methods for treating diseases in humans and vertebrate animals are provided using competitive antagonists of cellular metabolites combined with a protective agent for protecting host cells from toxic effects of the drugs. Also provided are kits comprising competitive antagonists and suitable protective agents. In addition, screening methods for identifying competitive antagonists, protective agents and potentiating agents, for use according to the methods of the invention, are provided.
Claims10
A method for treating a subject having a cancer or infectious disease comprising:
- (a) administering to the subject a competitive antagonist of adenine or methionine in an amount effective to treat the cancer or infectious disease, wherein the competitive antagonist of adenine is a substrate for a phosphoribosyltransferase selected from the group consisting of adenine phosphoribosyltransferase (APRT), hypoxanthine-guanine phosphoribosyltransferase (HGPRT), orotate phosphoribosyltransferase (OPRT), quinolinate phosphoribosyltransferase (QPRT), nicotinate phosphoribosyltransferase (NAPRT) and nicotinamide phosphoribosyltransferase (NAMPRT);
- and
- (b) administering to the subject a protective agent in an amount effective to increase the level of adenine or methionine in a population of host cells of the subject, thereby reducing the toxicity of the competitive antagonist to the subject, wherein the subject has a methylthioadenosine phosphorylase (MTAP) negative target cell and wherein the protective agent is a MTAP substrate.
A method for selective protection of a MTAP positive host cell exposed to a competitive antagonist of adenine or methionine, comprising contacting the host cell with a protective agent in an amount effective to increase the level of adenine or methionine in the host cell thereby reducing the toxicity of the competitive antagonist to the host cell, wherein the competitive antagonist of adenine is a substrate for a phosphoribosyltransferase selected from the group consisting of adenine phosphoribosyltransferase (APRT), hypoxanthine-guanine phosphoribosyltransferase (HGPRT), orotate phosphoribosyltransferase (OPRT), quinolinate phosphoribosyltransferase (QPRT), nicotinate phosphoribosyltransferase (NAPRT) and nicotinamide phosphoribosyltransferase (NAMPRT), and wherein the protective agent is a MTAP substrate.
Dependencies are inferred from the claim text.