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DOT - Despite the availability of eight nucleoside analogs for the treatment of HIV infections, toxicity and virus breakthrough remain significant concerns. There is a need for safer, orally bioavailable once-a-day drugs that are thymidine kinase (TK)-dependent and effective against thymidine analog mutations (TAMs) and multidrug resistant (MDR) HIV. DOT was found to have unique and surprising virologic and pharmacologic properties for a thymidine analog. DOT was markedly effective against numerous clinically relevant drug resistant mutants, including HIV containing MDR and T69S insert mutations. DOT was licensed to Pharmasset, Inc. in early 2006 and is currently in advanced preclinical trials as a prodrug.
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