Title/Topic:	Agouron reports novel anti-HIV compounds
Source:   	OTC  10/20/93 7:26 AM 
Author:	Jeffrey Herwatt
Date:	06:50 PM Today

               
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Agouron reports novel anti-HIV compounds

LA JOLLA, Calif., Oct. 20 /PRNewswire/ -- In a presentation at the 33rd 
Interscience Conference on Antimicrobial Agents and Chemotherapy i New Orleans, 
Agouron Pharmaceuticals Inc. (NASDAQ-NMS: AGPH) revealed the chemical structure 
of a novel class of orally bioavailable chemical compounds which potently 
inhibit a key enzyme required for replication of HIV and which, as a result, 
halt HIV infection of T lymphocytes in vitro. 
   Agouron scientist Krzysztof Appelt, Ph.D., described in atomic detail the de 
novo design of a previously unknown class of inhibitors of the enzyme HIV 
protease by a team of Agouron scientists working in cooperation with scientists 
at Eli Lilly.  Guided by x-ray generated snapshots revealing precisely how each 
new compound in the novel series fits into a critical "active site" cleft on 
the surface of the enzyme, the Agouron research team incrementally achieved a 
60,000-fold enhancement in the potency of the first compound in the series.  
The result, a compound designated AG1284, inactivated the enzyme with a potency 
equivalent to that of the most potent inhibitors of HIV protease previously 
reported.  In preclinical in vivo experiments, oral  administration of AG1284 
resulted in plasma levels of the compound  several-fold higher than the minimum 
concentration required for in vitro  anti-HIV activity of the compound. 
   Dr. Appelt characterized the results of the research program as a strong 
testimony to the power of protein structure-based drug design. "We have today 
presented details of the step-by-step design and optimization of one series of 
very novel HIV protease inhibitors which we regard as having significant 
clinical potential," said Dr. Appelt. "But we have used this same protein 
structure-based design methodology to generate other novel HIV protease 
inhibitors with completely different chemical structures whose preclinical 
performance appears to equal or to exceed that of this first series of Agouron 
compounds or, for that matter, the preclinical performance of any HIV protease  
inhibitor yet reported by others working in this field.  We believe it is in 
this ability to generate multiple development candidates, each of a completely 
different chemical character, that the special strength of protein 
structure-based drug design lies." 
   "We are encouraged and excited by the preclinical research results reported 
today in New Orleans, but we wish to sound a general caution against premature 
expectations for anti-HIV agents based solely upon preclinical data," said 
Peter Johnson, the company's president and chief executive officer. 
   Agouron Pharmaceuticals Inc. is a pioneer and leader in a 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-                        10/20/93 /CONTACT:  Peter Johnson, president and 
CEO, or Donna Nichols, director, corporate communications, of Agouron Pharmaceut
icals, 619-622-3009/ 
   (AGPH)  CO:  Agouron Pharmaceuticals Inc. ST:  California IN:  MTC SU: 
    Copyright 1993