Agouron Pharmaceuticals Inc. today was to announce that itsscientists have designed an enzyme inhibitor that has shownanti-tumor activity in animal studies.
The compound, AG-331, is a new inhibitor of thymidylatesynthase. TS is a building block of DNA that is responsible forthe rapid proliferation of cells.
Using protein structure-based drug design, the researcherscreated a synthetic chemical compound that selectivelyinactivates TS by blocking a functionally important cavity onthe surface of the enzyme. AG-331 and its analogs arechemically different from any class of substances previouslyknown to interact with TS, said Michael Varney, lead author ofthe scientists' report in the latest issue of the Journal ofMedicinal Chemistry.
According to data to be presented later this month, a group ofsix mice with murine lymphoma given twice-daily doses of AG-331 for 10 days had a 216 percent average increased life spancompared with 11 control animals. The treated mice had amean survival time of 55 days compared with 25 days foruntreated mice.
In addition, three of the treated animals were alive at the endof the 100-day evaluation period, while all the control animalshad died.
The San Diego company (NASDAQ:AGPH) plans to file aninvestigational new drug application with the FDA later thisyear to begin Phase I trials of AG-331 for a number of solidtumor indications.
Agouron has designed seven series of TS inhibitors. Anothercompound, AG-85, is in pilot studies in psoriasis patients as atopical treatment.
The anti-tumor data is to be presented March 18 at asymposium in Amsterdam, the Netherlands, sponsored by theNational Cancer Institute and the European Organization forResearch on Treatment of Cancer.
Agouron shares closed up 13 cents on Tuesday at $14.25.
-- Karen Bernstein BioWorld Staff
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