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UI-led study shows experimental anti-cancer drug also has anti-HIV properties

The results of a study led by a University of Iowa researcher suggest that a drug already undergoing stage I and II clinical trials as a cancer treatment may also have potential as an anti-HIV therapy.

The study, led by David Price, Ph.D., a UI professor of biochemistry working with Matija Peterlin at the University of California San Francisco and Adrian Senderowicz at the National Cancer Institute, found that very low concentrations of flavopiridol, a drug manufactured by Aventis Inc., blocks HIV-1 replication in cell culture experiments. These findings appeared in the July 21 online issue of the Journal of Biological Chemistry.

Flavopiridol strongly hinders the cellular process known as transcription, a multi-step process which results in the production of ribonucleic acid (RNA). Cells use the genetic information encoded by these long RNA molecules to make proteins.

Flavopiridol effectively blocks the action of an enzyme called P-TEFb, which controls one of the steps in the transcription process. In fact, flavopiridol is the most powerful P-TEFb inhibitor to date. In Price's test tube experiments, even extremely low concentrations of flavopiridol were effective at blocking the action of P-TEFb.

P-TEFb is required for transcription of the HIV-1 genome to occur. Flavopiridol inhibits P-TEFb, causing inhibition of transcription. In tests to investigate its effect on HIV-1 infection and viral spread in cultured human cells, Price's team found that the same low concentrations of flavopiridol that inhibited P-TEFb dramatically blocked HIV-1 infection and replication.

"Since P-TEFb is a key factor in HIV-1 infection and flavopiridol blocks HIV-1 propagation in culture, we believe that this substance should be tested as a potential anti-AIDS drug," Price said.

During infection, HIV-1 undergoes mutations in its DNA that allow its proteins to change and become resistant to drugs. This is one of the biggest problems with treatment of HIV. Many
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Contact: Jennifer Brown
brownj@mail.medicine.uiowa.edu
319-335-9917
University of Iowa
2-Aug-2000


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