Researchers at The Upjohn Co. are developing a new class ofpotential AIDS drugs that block replication of the virus, butare safer and chemically distinct from existing nucleosideinhibitors.
Reporting this week in the Proceedings of the NationalAcademy of Sciences, Upjohn scientists and collaborators atMount Sinai medical center in Miami and the University ofMiami, Fla., described the action of aryl piperazines ininhibiting reverse transcriptase, the enzyme that HIV, theAIDS virus, uses to insert itself into the host cell's DNA.
The new inhibitors are safe because they only block normalcell functions at concentrations a hundredfold to athousandfold stronger than those that stop viral reversetranscriptase, the researchers showed.
Nucleoside inhibitors such as AZT and ddI, which have shownside effects such as anemia, are much more likely to interferewith important cellular enzymes.
The new inhibitors potently blocked HIV replication in whiteblood cells grown in the lab. And in a study conducted withSystemix Inc. (NASDAQ:STMX) of Palo Alto, Calif., the Upjohnresearchers showed that their inhibitors could protect SCID-humice from infection with HIV.
However, AZT was better at protecting the immune-deficient mice. None of the five SCID-hu mice given AZT intheir drinking water showed HIV infection after exposure tothe virus. But only three of eight mice given the mostpromising of the aryl piperazines orally, twice daily, resistedinfection.
Combinations of nucleoside and the new non-nucleosideinhibitors show a synergistic effect against HIV infection, theresearchers said.
The inhibitors were discovered by screening 1,500 chemicalsin the Kalamazoo, Mich.-based company's inventory.
-- Roberta Friedman, Ph.D. Special to BioWorld
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