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AGOURON SCIENTISTS REPORT RATIONAL DESIGN OF NEW ANTI-TUMOR DRUG

 AGOURON SCIENTISTS REPORT RATIONAL DESIGN OF NEW ANTI-TUMOR DRUG
 SAN DIEGO, March 11 /PRNewswire/ -- Scientists from Agouron Pharmaceuticals Inc. (NASDAQ-NMS: AGPH) have reported in the most recent issue of the Journal of Medicinal Chemistry details of the rational design of a potent new synthetic drug which blocks a key enzyme involved in the proliferation of tumor cells. At an international symposium on new drugs for cancer therapy to be held in the Netherlands next week, Agouron scientists will report significant anti-tumor activity in test animals demonstrated by the drug designated AG-331.
 The subject of these scientific reports is a potent inhibitor of the enzyme thymidylate synthase ("TS"). TS plays an essential role in cellular proliferation; inhibition of TS results in the selective death of tumor cells. Using a technology described as "protein structure- based drug design," Agouron scientists designed a synthetic chemical compound which, at very low concentrations, selectively inactivates TS by blocking a functionally important cavity on the surface of the enzyme. "AG-331 and its analogs are chemically very different from any class of substances previously known to interact with TS," said Michael D. Varney, Ph.D., lead author of the J. Med Chem. article (1992, 35, 663-676). "We consider the design of this compound to be a consummate example of the power of protein structure-based drug design to generate chemically novel, biologically active agents."
 In a separate report to be presented March 18 at an international symposium in Amsterdam sponsored by the National Cancer Institute (U.S.) and the European Organization for Research on Treatment of Cancer, Agouron pharmacologists will report results of their biological studies of AG-331. In these studies AG-331 demonstrated significant anti-tumor activity in vitro, killing a range of cultured human and murine tumor cells, including cells known to possess one of the most common mechanisms of drug resistance. In subsequent studies in vivo, administration of twice-daily doses of AG-331 (17.5 mg/kg) resulted in 216 percent average increased life span of test animals with murine lymphoma. Extensive preclinical toxicological studies of this compound are currently in progress. AG-331 is expected to be the subject of an Investigational New Drug (IND) application to be filed by Agouron with the Food and Drug Administration later this year.
 Agouron Pharmaceuticals Inc. is a pioneer and leader in a new technology for the rational design of novel synthetic drugs based upon the molecular structures of proteins which play key roles in human disease. Agouron is currently applying this technology to the design and development of drugs for treatment of cancer, AIDS and other serious diseases.
 -0- 3/11/92
 /CONTACT: Peter Johnson, president and CEO, or Donna Nichols, manager of corporate communications, 619-622-3000, both of Agouron Pharmaceuticals/
 (AGPH) CO: Agouron Pharmaceuticals ST: California IN: MTC SU:


SE-JL -- SD001 -- 7190 03/11/92 09:04 EST
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Publication:PR Newswire
Date:Mar 11, 1992
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