      Document 0001
 DOCN  DRG0001
 UNIQUE IDENTIFIER        DRG-0246
 NAME OF SUBSTANCE        2-Fluoro-2',3'-dideoxyadenosine [Fundam Appl
                          Toxicol 1995 Sep;27(2)]
 REGISTRY NUMBER          114849-59-1
 SYNONYMS                 F-ddA [Fundam Appl Toxicol 1995 Sep;27(2)]
 SYNONYMS                 beta-Fluoro-ddA [NCI 95 C-192]
 SYNONYMS                 beta-F-ddA [Biochem Pharmacol 1994 Oct
                          7;48(7)]
 PROTOCOL ID NUMBERS      NCI 95 C-192
 SECONDARY SOURCE ID      NSC-613792 [NCI 95 C-192]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Similiar to dideoxyadenosine
                          (ddA), except that a fluorine atom is
                          introduced into the 2'-position of the
                          glycon. Like ddA and its metabolite ddI,
                          beta-F-ddA is metabolized intracellularly to
                          a triphosphate moiety that acts as a reverse
                          transcriptase inhibitor. Because of the
                          fluorine substitution, beta-F-ddA is expected
                          to be absorbed better than didanosine because
                          the fluorinated molecules become more stable
                          to acid conditions. beta-F-ddA has
                          demonstrated anti-HIV activity in vitro.
                          beta-F-ddA does not appear to have cross
                          resistance with ddI or other nucleoside
                          analogues, and is even active against strains
                          of HIV that have multi-dideoxynucleoside
                          resistance associated with a mutation at
                          codon 151 of reverse transcriptase. In
                          comparison with zalcitabine, beta-F-ddA is
                          22000 times less potent in suppressing
                          cellular mitochondrial DNA synthesis, while
                          anti-HIV potency is only modestly less
                          compared to the unfluorinated compound.
                          Inhibition of mitochondrial DNA could be
                          responsible for the delayed clinical toxicity
                          sometimes observed with dideoxynucleosides.
                          [NCI 95 C-192; Biochem Pharmacol 1994 Oct
                          7;48(7)]
 DISEASES STUDIED/TREATED HIV infection [NCI 95 C-192]
 CLASSIFICATION CODE      Antiviral [Fundam Appl Toxical 1995
                          Sep;27(2)]
 ADVERSE EFFECTS          Has shown cardiotoxicity in rats. [Fundam
                          Appl Toxicol 1995 Sep;27(2)]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Fluorinated analogue of
                          didanosine; a purine dideoxynucleoside. [NCI
                          95 C-192; Fundam Appl Toxicol 1995 Sep;27(2)]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [NCI 95 C-192]
 MANUFACTURERS            Drugs are provided by each participating unit
                          site
 REFERENCES               MED/95032193. Tsai CH, Doong SL, Johns DG,
                          Driscoll JS, Cheng YC. Effect of anti-HIV
                          2'-beta-fluoro-2', 3'-dideoxynucleoside
                          analogs on the cellular content of
                          mitochondrial DNA and on lactate production.
                          Biochem Pharmacol. 1994 Oct 7;48(7):1477-81.
 ENTRY MONTH              9606
 LAST REVISION DATE       960612
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
