title: 4'-Ethynylstavudine (4'-Ed4T) has potent anti-HIV-1 activity with reduced toxicity and shows a unique activity profile against drug-resistant mutants.
abstract: A nucleoside analogue 4'-ethynylstavudine (4'-Ed4T) was recently synthesized during chemical studies directed towards the development of a new route to 4'-carbon-substituted nucleosides. This compound was found to be more anti-HIV-1 active than the parent compound stavudine (d4T) and much less toxic to various cells and also to mitochondrial DNA synthesis. It became apparent that 4'-Ed4T is a better substrate for human thymidine kinase than d4T, and very much more resistant to catabolism by thymidine phosphorylase. The study of 4'-Ed4T against various drug-resistant HIV-1 mutants has disclosed its unique activity profile.
authors.affiliation: School of Pharmaceutical Sciences, Showa University, Tokyo, Japan. hirotnk@pharm.showa-u.ac.jp
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Haraguchi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kumamoto
authors.forename: Masanori
authors.initials: M
authors.lastname: Baba
authors.forename: Yung-Chi
authors.initials: YC
authors.lastname: Cheng
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000378:metabolism; D024882:Drug Resistance, Viral / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D015394:Molecular Structure; D009154:Mutation; D018119:Stavudine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013937:Thymidine Kinase / Q000378:metabolism; D013939:Thymidine Phosphorylase / Q000378:metabolism
chemical_list: C505960:4'-ethynylstavudine; D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D018119:Stavudine; D013939:Thymidine Phosphorylase; D013937:Thymidine Kinase