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Research Magazine > ARCHIVE > Summer 01 > Article

Hits and Misses
by Paul Karr

David Chu and his research team have synthesized more than 1,000 compounds during his 19 years at the university, and some have shown great promise as potential antiviral and anticancer agents — a level of productivity all the more impressive in an academic setting, “where you have many other academic priorities as a professor,” Chu said. Some of the most promising clinical candidates to come out of his and his research collaborators’ laboratories include:

  • L-FMAU (Clevudine): an anti-hepatitis B virus agent
    Discovered: 1993 in collaboration with Y.C. Cheng of Yale University
    Licensed by: an undisclosed biotechnology company and Bukwang
    Pharmaceuticals, Seoul, South Korea
    Status: Phase I/II dose-range finding study

In laboratory studies, small doses of L-FMAU can stop the spread of the hepatitis B virus in its tracks. Subse-quent animal tests have demonstrated potent antiviral properties in the woodchuck animal model. The woodchuck is susceptible to the woodchuck hepatitis B virus, a disease that closely resembles hepatitis B in humans. The most striking results in the woodchuck studies — unlike results from other antiviral agents under development for hepatitis B virus — are the profound antiviral effects and the minimal “rebound” after treatment with L-FMAU. Recent preliminary Phase I trials of L-FMAU in humans suggest that the animal data may reflect the human trials, although it is too early to determine the full potential of this compound.

  • DAPD: an anti-HIV and anti-hepatitis B virus agent
    Discovered: 1992 in collaboration with R.F. Schinazi of Emory University/VA Medical Center
    Licensed by: an undisclosed biotechnology company
    Status: Phase II clinical trials

DAPD shows promise for the treatment of HIV-infected patients. It acts swiftly against both HIV and hepatitis B virus, complements other HIV therapies to which the virus can become resistant and seems to work synergistically. No serious side effects were detected during initial trials. In view of these promising results, the Food and Drug Administration placed DAPD on the “fast track” list of compounds for development.

  • CS-87: anti-HIV agent
    CS-92: anti-HIV agent
    Discovered: 1987-1988 in collaboration with Schinazi
    Status: trials discontinued

Chu’s team discovered these two compounds in the late 1980s, and they received national attention as promising drugs in the treatment of HIV.

Other promising drugs to come out of the lab include:

  • L-IOddU: an anti-Epstein-Barr virus agent
    Discovered: 1995
    Licensed by: Achillion Pharmaceuticals Inc., New Haven, Conn.
    Status: preclinical stages
  • L-OddC (Troxacitabine): an anti-cancer agent
    Discovered: 1993 in collaboration with Cheng
    Licensed by: Biochem Pharma, Quebec City, Canada
    Status: early Phase III trials


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AZT is an effective FDA-approved nucleoside drug against HIV. The illustration above shows how well the active form of AZT binds to the active site of an HIV enzyme. Scientists believe the better the attachment, the more effective the drug. Photo courtesy of David Chu