Learn More
Matrix metalloproteinase-13 (MMP13) is a Zn(2+)-dependent protease that catalyzes the cleavage of type II collagen, the main structural protein in articular cartilage. Excess MMP13 activity causes cartilage degradation in osteoarthritis, making this protease an attractive therapeutic target. However, clinically tested MMP inhibitors have been associated(More)
5-Lipoxygenase (5-lipox) has been purified to homogeneity from the 20,000 xg supernatant of sonicated rat basophilic leukemia (RBL-1) cells using a 4-step procedure. Purification was achieved primarily through the use of anion-exchange HPLC on two different media. Using the supernatant from 1 X 10(9) cells, approximately 33 micrograms of the enzyme can be(More)
N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) is an essential enzyme in aminosugars metabolism and an attractive target for antibiotic drug discovery. GlmU catalyzes the formation of uridine-diphospho-N-acetylglucosamine (UDP-GlcNAc), an important precursor in the peptidoglycan and lipopolisaccharide biosynthesis in both Gram-negative and(More)
Two isoforms of the cyclooxygenase (COX) enzyme have been identified: COX-1, which is expressed constitutively, and COX-2, which is induced in inflammation. Recently, it has been shown that selective COX-2 inhibitors have antiinflammatory activity and lack the GI side effects typically associated with NSAIDs. Initial mass screening and subsequent SAR(More)
N-Arylanthranilic acids, known generically as the fenamates, are nonsteroidal antiinflammatory drugs (NSAIDs) that block the metabolism of arachidonic acid by the enzyme cyclooxygenase (CO). Substitution of the carboxylic acid functionality of several fenamates with acidic heterocycles provided dual inhibitors of CO and 5-lipoxygenase (5-LO) activities when(More)
For an animal model to predict a compound's potential for treating human disease, inhibitor interactions with the cognate enzymes of separate species must be comparable. Rabbit and human isoforms of stromelysin-1 are highly homologous, yet there are clear and significant compound-specific differences in inhibitor potencies between these two enzymes. Using(More)
Throughout the drug discovery process, discovery teams are compelled to use statistics for making decisions using data from a variety of inputs. For instance, teams are asked to prioritize compounds for subsequent stages of the drug discovery process, given results from multiple screens. To assist in the prioritization process, we propose a desirability(More)
Selective cyclooxygenase-2 (COX-2) inhibitors have been shown to be potent antiinflammatory agents with fewer side effects than currently marketed nonsteroidal antiinflammatory drugs (NSAIDs). Initial mass screening and subsequent structure-activity relationship (SAR) studies have identified 4b (PD138387) as the most potent and selective COX-2 inhibitor(More)
  • 1