Combination therapies to treat methylthioadenosine phosphorylase deficient cells

摘要

"COMBINATION THERAPIES TO TREAT DEFICIENT CELLS IN METHYLTOADENOSINE PHOSPHORYLASE". The present invention relates to combination therapies for treating proliferative cell disorders associated with methylthioadenosine phosphorylase (MTAP) deficient cells in a mammal. Combination therapies selectively kill MTAP-deficient cells by administering an inosinate de novo synthesis inhibitor and administering an antitoxicity agent, wherein the inosinate de novo synthesis inhibitors are glycine amide ribonucleotide formyltransferase ("GARFT") inhibitors and / or aminoimidazolcarboximide ribonucleotide formyltransferase ("AICARFT"), and the antitoxicity agent is an MTAP substrate (e.g., methylthioadenosine or "MTAP"), an MTA precursor, an analogue of an MTA precursor or a prodrug of an MTAP substrate.