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Some claim that Broadway, the old downtown is not to be incorporated within the new downtown; it is near it but has been sort of cauterised off from it. The street pulses with the musics of the latino world from a thousand loudspeakers; the Mexican, Mariachi; Colombian Salsa, Cumbia, Gaita, the Dominican Republic Merengue big ornate old cinemas showing Latino films, some put to other uses; one great old barn advertises EVANGELIZACION. I remember pausing in a big echoey Gallery packed with stalls, the sun filtering in though the iron pillars that supported it, listening to a sweet shuffly cumbia and feeling so good. With disease pathways allowed a more rational approach where analogues of natural ligands could be designed. Around 10 years ago, drug discovery programs refocused their technology on the rapid assay of huge numbers of compounds. This random approach is called high-throughput screening, and aims to identify compounds with IC50s lower than 10 mM for their target proteins. The advent of this new technology required huge investment in faster systems for compound synthesis for the generation of large chemical libraries. Combinatorial chemistry was developed using both solid phase chemistry approaches, and solution phase libraries coupled with high-throughput purification platforms Bailey 1997; Spencer 1998; Seneci & Miertus 2000; Dolle 2004 ; . Automation of bioassays and systems for collection, storage and analysis of the very large datasets generated were also developed. However, the rate of newly registered compounds in clinical trials has not increased in proportion to the exponential increase in investment occasioned by these new robotic approaches. The industry has, therefore, once again refocused, this time on targets and their related family members that are thought to be more tractable. Tractability of a target is based on the number of drug-like ligands for a target class, as well as knowledge of the binding sites of family members using protein structure information Hopkins & Groom 2002 ; . Examples of families of interest include the protein kinases and various proteinases. The classification of targets into families has allowed the design of focused compound libraries for particular families. Several approaches are now concentrating on screening very small molecules, or `fragments' from which a lead can be designed using a knowledge, derived from biophysical assays, of how the fragment binds in the active site of the target. In parallel, in silico approaches for identifying potential drug candidates have been developed. Ligand docking aims to find the optimum binding position and orientation for a compound in the active site of the proteins Taylor et al. 2002 ; . The best docking programmes correctly dock about 7080% of ligands when tested on large sets of proteinligand complexes Nissink et al. 2002; Friesner et al. 2004 however, difficulties arise in trying to predict the affinities of the different compounds for the protein active site Kitchen et al. 2004 ; . Nevertheless, virtual screening has proved helpful in docking and ranking a large number of compounds so that the highest-ranking compounds can be selected for acquisition or synthesis and experimentally tested for activity against the target protein. Virtual screening provides a significant enrichment, perhaps twentyfold, of true hits in a selected subset of compounds Boehm et al. 2000; Abagyan & Totrov 2001; Bajorath 2002; Lyne 2002; Shoichet et al. 2002; Jain 2004; Kitchen et al. 2004 ; . Both the fragment based approach and virtual screening are designed to provide more efficient sampling of chemical space by effectively decreasing the compound sample size. This optimization of the small molecule screening process has allowed experimental methods such as NMR and X-ray crystallography to contribute to drug discovery. Fragments are.

Anuja Jhingran, MD Division of Radiation Oncology University of Texas, M.D. Anderson Cancer Center Houston, Texas 10 minutes.
CRC CF: Cognitive function and fatigue in cancer patients after chemotherapy: a longitudinal controlled study in patients with colorectal cancer. The MAX Study: A phase II III study to evaluate the role of Mitomycin C, Avastin and Xeloda in patient with untreated metastatic colorectal cancer. PRODIGE: A Trial of Dalteparin Low Molecular Weight Heparin for Primary Prophylaxis of Venous Thromboembolism in Brain Tumour Patients. ProPIT: A randomised phase II study of two dose schedules of PI88 in combination with docetaxel in patients with androgenindependent prostate cancer AIPC and baraclude.

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