Agouron Pharmaceuticals Inc. announced Friday that itsresearchers have solved the three-dimensional atomicstructure of rhinovirus 3C protease (RVP), an enzyme thecompany said plays a vital role in the replication of virusesresponsible for common upper respiratory infections includingthe common cold.
As part of its expanded collaboration with the pharmaceuticaldivision of Japan Tobacco Inc. (JT), Agouron has begun to use arational drug-design process to design anti-rhinoviral agentsbased on the RVP structure.
Peter Johnson, Agouron's president and chief executive officer,told BioWorld that the La Jolla, Calif., company plans to submitits findings on the RVP structure to a peer-reviewed journal forpublication, even though he noted that Agouron would notpublish all the atomic coordinates mapped out by itsresearchers over the past several years.
Mapping (or solving) the molecular structure of proteins is oneof Agouron's core technologies. Its lead therapeutic candidates,AG-337 and AG-331, are both designed to match the structureof thymylate synthase enzyme. The agents are being developedfor the treatment of solid tumors and are expected to beginPhase II clinical trials by the middle of the year, Johnson said.
The process of mapping proteins involves the cloning andexpression of the enzyme in question, after which the protein iscrystalized and put through a laborious process of X-raydefraction analysis. Locating all the atoms in the crystalineprotein of RVP took about two-and-a-half years, Johnson said.
The researchers' findings were announced Friday at a scientificconference in Santa Fe, N.M., that was sponsored by theKeystone Symposia. Agouron's senior research fellow, DavidMatthews, also revealed that the company has identified the"critical cleft" on the surface of the RVP enzyme responsible forthe biochemical activity of the protein.
Agouron (NASDAQ:AGPH) plans initially to design drugs for thetreatment or prevention of rhinovirus infections in patientswith chronic obstructive pulmonary disease, such asemphysema and chronic bronchitis. The company's solution ofRVP, Johnson noted, was "a strong part of (JT's) interest inteaming up with us and extending their agreement." On Feb. 28,Agouron announced that JT would extend its collaboration withAgouron up to a total potential investment of $56 million (seeBioWorld, March 1).
Agouron's stock jumped $2.25 a share on Friday, closing at$14.75.
-- Karl A. Thiel Business Editor
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