Sites of interest on the World Wide Web–edited by Rick Neubig

Drug Metabolism

Two major components of pharmacology are pharmacokinetics and pharmacodynamics. The former is greatly influenced by a large family of enzymes termed the cytochromes P450, which modify drug molecules, xenobiotics, and endogenous compounds. A online resource about P450s can be found at Dr. David Nelson’s Website at the University of Tennessee (http://drnelson.utmem.edu/CytochromeP450.html). It provides links to gene and protein sequences, to the Online Mendelian Inheritance in Man (OMIM) database, and the LocusLink database (for example, http://www.ncbi.nlm.nih.gov/LocusLink/list.cgi?Q=P450&ORG=Hs&V=0), which warehouses the mapped chromosomal locations of each P450 as well as provides hyperlinks to other useful databases. Nelson’s Website also has links to recent scientific meetings regarding P450s.

Of clinical interest, the different P450 enzymes that are most important in the metabolism of different drugs, and the effects that drugs have on the activity or expression of the P450 isozymes, are listed at www.drug-interactions.com, which is maintained by Dr. David Flockhart at the University of Indiana. He also sells a convenient “Drug Interactions” card for clinical pharmacologists to identify and avoid drug interactions with cytochromes P450. As he states on his Website: “Specifically, if a prescriber is aware of the dominant cytochrome P450 isoform involved in a drug’s metabolism, it is possible to anticipate, from the inhibitor and inducer lists for that enzyme, which drugs might cause significant interactions. The laminated card table is focused on clinically relevant interactions, and is updated at least twice yearly.”

Signal Transduction Resources

The other side of the pharmacology coin is pharmacodynamics, and signal transduction plays a major role in the actions of drugs. Protein kinases have been garnering much attention recently as potential drug targets. A Protein Kinase Resource (http://pkr.sdsc.edu/html/index.shtml) is a user-curated database on many different types of protein kinases. It also provides links to meetings, kinase researchers, and web-based educational information on protein kinases.

A greater amount of information on signal transduction pathways is available at Cell Signaling Technology’s commercial Website (http://www.cellsignal.com/retail/reference/index.asp?cookie%5Ftest=1). In addition to selling signaling reagents, their useful pathway maps cover the known molecular interactions in apoptosis, glucose metabolism, chromatin remodeling, and cell cycle checkpoints. Information on protein modules located in signaling proteinscan also be found there.

Finally, a real-world resource for cDNA clones of proteins involved in G protein systems can be found online at the Guthrie Institute cDNA Resource (http://www.guthrie.org/cdna/). They supply human cDNAs for nearly all G protein ? subunits in wild-type, mutant, or epitope-tagged forms, and also provide several cDNAs that encode low molecular mass Ras superfamily proteins, some G protein-coupled receptors, and the family of human regulators of G protein signaling (RGS proteins).

Obesity 101

The review article on pages _ - _ by Hosoda et al. discusses the potential role of the Growth Hormone release-stimulating hormone (Ghrelin) in obesity and how its receptor (GHS receptor) might be a useful target for antiobesity therapeutics. A Website that contains much information about obesity news and possible new obesity drugs is http://obesity-101.com. Although much of their information requires a paid subscription, they do have many links that are accessible without subscription (especially http://www.obesity-news.com/inuse.htm and http://www.obesity-news.com/newdrugs.htm) making it worth a virtual visit.

Want to know more about clinical trials testing the efficacy of new drugs for the treatment of obesity or other disorders? Two sites, http://clinicaltrials.gov and http://www.centerwatch.com/, provide searchable databases of ongoing or recently completed clincal trials. Both are easily searched to find particular disorders (such as obesity) or other criteria such as the geographical location of the trials.