engleski

Combinatorial Chemistry and Technology: Current trends and initiatives – Croatia – country report

High Throughput Screening – Recent Trends in Drug Discovery Process Donatella Verbanac Head of Screening Unit at Discovery Division ; Pliva d.d. Pharmaceutical Industry, incorporated ; Prilaz baruna Filipovića 25, 10 000Zagreb The year 2000 has been the landmark year for the science and medicine. It will leave an indelible mark on the process of drug discovery, as well. The drugs developed over the last four decades are targeted at about 500 different biological targets. With the sequencing of the human genome, over 100, 000 new biological targets will be recognized. It has been estimated that at least 10 % of them could be used as targets for drugs. This will bring additional problems to be solved for an already “over- spread out” drug industry. High throughput screening (HTS) is system for analyzing compound libraries and natural products in order to identify new therapeutic hits and leads on potential targets. HTS arose in 1990s as 96 well microtitre plates took over from test tubes as the receptacle of choice for biological assays. In combination with combinatorial chemistry it resulted in a paradigm shift from knowledge-based sequential synthesis and testing to parallel processing of multiple compounds. With the objective to improve success rates and cycle times for discovering new hits, HTS is set to become one of the cornerstones of drug discovery. Combinatorial chemistry, genomics and high throughput screening are resulting in many-fold increases in the number of compounds that must be evaluated by drug discovery teams. In response to the rapidly changing discovery paradigm, it is important to consider preclinical properties at the earliest stages to assist in compound prioritization and to avoid downstream failure as related to drug delivery, pharmacokinetic or toxicological performance. Implementing screens for physicochemical properties (e.g. ID/purity, stability, solubility, permeability) and in vitro metabolism, can provide data to prioritize hits and leads in favor of those most likely to possess acceptable preclinical properties. The design of these assays must appropriately balance throughput, accuracy and cost depending upon the intended objective and at what phase of this discovery process the data are needed. Our experience in developing an integrated approach in providing these data, challenges for selected assays, and application to hit-set deconvolution will be described.

Combinatorial Chemistry; High troughput Screening; Compound Bank; Cell-based assays; microbiology testing; enzymes

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