Combination therapies for treating methylthioadenosine phosphorylase deficient cells

• Main Authors: BORITZKI, THEODORE JAMES, SKALITZKY, DONALD JAMES, KUNG, PEI-PEI, LUKE RAYMOND ZEHNDER, JERRY JIALUN MENG, BLOOM, LAURA ANNE, OGDEN, RICHARD CHARLES, LESLIE ANN KUHN
• Format: Patent
• Language: Chinese; English
• Published: 01.10.2003
• Subjects: HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The present invention is directed to combination therapies for treating cell proliferative disorders associated with methylthioadenosine phosphorylase(MTAP) deficient cells in a mammal. The combination therapies selectively kill MTAP-deficient cells by administering an inhibitor of de novo inosinate synthesis and administering an anti-toxicity agent, wherein the inhibitors of de novo inosinate synthesis are inhibitors of glycinamide ribonucleotide formyltransferase ("GARFT") and/or aminoinidazolecarboximide ribonucleotide formyltransferase ("AICARFT"), and the anti-toxicity agent is an MTAP substrate (e.g. methylthioadenosine or "MTA"), a precursor of MTA, an analog of an MTA precursor or a prodrug of an MTAP substrate.