NEWS OF THE WEEK DRUG
DISCOVERY
contribution to the ADME area by making the MetaSite software available via an Internet download {fromwww.moldiscovery.com} at no costforacademic and noncommercial use. The group has made using MetaSite as easy as possible for medicinal chemists." Tudor I. Oprea, chief of the division of biocomputing at the University of New Mexico School of hand, predicts compound meta- Medicine, calls MetaSite "a major bolic sites and identifies the cy- breakthrough in our understandtochrome P450 involved with ing of small molecule-cytochrome about 80% accu0 P450 interactions. racy and takes only 1 To my knowledge, a few seconds per | it's thefirstin silico compound to do so. I method that predicts Required input is | with at least 70%, a 2-D structure of | but mostly 80% or the compound and I higher, accuracy 3 3-D structures of the site of metabothe enzymes, which lism and inhibition are already known of small molecules for the major hurelated to P450 enman cytochrome zymes. True predicP450s. tivity is achieved, regardless of chemical Christopher A. class." Lipinski, discov- Cruciani erer of the Lipinski For preclinical rules for predicting compounds' drug discovery, he adds, "Metapotential as drugs, says: "Cruciani Site should be on every desktop. It and his group have made a valuable is that important."—STU BORMAN
FINDING DRUG METABOLIC SITES
Computational technique predicts how drug compounds will break down
A
SOFTWARE PROGRAM THAT
could have a significant impact on drug discovery has been developed and tested by a European group. The program, MetaSite, predicts which part of a potential drug compound will be metabolized by one of the major human cytochrome P450 enzymes. It also predicts which cytochrome will catalyze the process. Cytochrome P450s are key enzymes in the elimination of drugs from the body. If knowledge of a compound's degradation site could be determined in advance, medicinal chemists could protect that site chemically and thus prolong the compound's lifetime in the body. Chemists could also use the information to prescreen new drug candidates for suitability, design prodrugs (uiactive compounds that become drugs when metabolized), or help assess a drug's ADME/Tox (absorption, distribution, metabolism, excretion, and toxicity) properties. MetaSite was conceived by Ismael Zamora of Lead Molecular Design, Sant Cugat del Vallès, Spain, and was codeveloped with chemistry professor Gabriele Cruciani's group at the University of Perugia, Italy, and researchers at Molecular Discovery in London, who now report on its capabilities (J. Med. Chem. 2005,48,6970). Cruciani and coworkers note that earlier computational techniques for predicting metabolic reaction sites are not generally used by pharmaceutical researchers because they're inaccurate, undependable, and difficult to carry out. MetaSite, on the other WWW.CEN-0NLINE.ORG
HURRICANE
AFTERMATH
Katrina's Damaging Floodwaters Not As Tonic As Feared
I
In early September, Pardue and coworkers n the wake of Hurricane Katrine, when Lake collected ftoodwater samples from the city's Pontchartrain breached its levees and fitted West End and Lakeview neighborhoods—an arthe low-tying city of New Orleans Ukee bathea where rescue efforts led to widespread expotub» public health officials feared floodwaters sure to floodwaters—and from the Tulane-Grawould expose residents and first responders to vier neighborhood. a brew of toxic chemicals and pathogenic origanisms. A newly published analysis» however, inPardue's team detected slightly elevated levdicates that those floodwaters were no more els of lead and gasoline, but these were simitoxic than the city's normal storm runoff {Envilar to those found in normal storm runoff and did ron, Sch TçctmoLt published online Oct. 11, dx.doi. not pose a major threat to human health. They org/10.1021/es0518631). found that the greatest potential risk to human health came from very elevated levels of fecal "What we had in New Orleans was basically a year's worth of storm water flowing through the city bacteria, probably from the city's overwhelmed in only a few days," says John H. Pardue, director of sewer system. the LouisianaWater Resources Research institute Pardue notes that the water pumped back into at Louisiana State University, Baton Rouge. "We still Lake Pontchartrain may pose a threat to aquatic don't think the floodwaters were safe, but it could life because of its low oxygen concentration and have been a lot worse, it was not the Chemical ca- the presence of heavy metals such as zinc and tastrophe some had expected," he adds. COpper.-BETHANY HALFORD C & E N / OCTOBER 17, 2005
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