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Have you ever pondered about how all those potent and titantic drugs get to the shelf? The birth of any drug begins during a process known as combinatorial chemistry. Combinatorial chemistry - used to generate millions of compounds - involves the random assembly of parts. A part in this context would constitute a reactive chemical part; assuming that there are 3 distinct parts each with three distinct forms, there would in theory be approximately 34 possible compounds. It is in such a manner that compounds are generated, typically by the millions with the knowledge that only about 3 or 4 of those millions will become potential drugs, and even fewer that will actually make it to the market.Now that the potential drugs have been generated, they must be subjected to screens or tests. Typically, drugs tend to target cell surface receptors known as GPCR (G-protein coupled receptor); however enzymes, nuclear receptors, ion channels, and signal transduction proteins are all drug targets as well. The G-Protein coupled receptors, found on the surface of cells, can activate a signaling cascade that results in the activation, and expression of a particular protein.At the molecular level, two types of tests are typically available: in vitro, and cell based assays (or in vivo). An in vitro screen typically utilizes the potential drug, the drug target, and an external detection system. The detection system is utilized in all cases to visualize events; non-isotopic detection methods (luminescence, colorimetry, resonance energy transfer, time resolved fluorescence, cell based fluorescence assays, fluorescence polarization, fluorescence correlation spectroscopy) are the most commonly utilized systems. Techniques such as fluorescence polarization, or fluorescence correlation spectroscopy are used to tackle problems such as quenching, autofluorescence, and photobleaching. The distinction between a cell based assay and an in vitro screen is that the cell based assay utilizes live cells - approximately 50 000 seeded onto the floor of the well - to verify the effect of a drug on the cell as a whole. Cell based assays are typically used to measure proliferation, toxicity, marker production, motility, activation of signaling pathways, and changes in morphology. In such cases, other factors such as 2D versus 3D culture, or static versus profusion cultures might contribute to the result obtained. When using cell based assays, the detection system is typically incorporated into the cell.In other words, the cells are altered in such a way as to produce a cell line with an incorporated detection system. For instance, in the case of the reporter gene assay, the target gene activated by the cascade is excised and replaced with a reporter gene such as luciferase. In this case, it is assumed that if the drug binds its target and activates the signaling cascade, that instead of activating the gene, it will activate the luciferase which will result in the emission of light which is visible to the naked eye, and that can be recorded. In another instance, the cell proliferation assay can be used to detect rates of proliferation. In this case, an electrical current is passed through the layer, and as the layer thickens, the current flow decreases; this decrease is detected and converted into proliferation rates.Compounds generated are subjected to multiple screens - from screens to test functionality to those that test toxicity. In the modern day, and age, drugs are screened by the millions, a process known as high throughput screening. High-throughput screening allows for the screening of millions of potential drugs in a relatively short period of time. In other words, about a million or so potential drugs can be screened in a day or so; this is achieved by a parallel method wherein millions of drugs are simultaneously tested using 94, 384, 1536, or 3456 wells are utilized. In fact, drugs must pass many a test before being considered for mass production, however, most drugs fail during toxicity testing. In fact, even if a drug passes toxicity screens in the lab on animals, it can fail during the clinical stage. Usually, a drug is taken out of clinical testing when it fails the toxicity tests. However, given the number of drugs that can be screened, and availability of theoretical compounds, we always run a good risk of finding that herculean drug. Article Tags: Cell Based Assays, Potential Drugs, Cell Based, Based Assays, Detection System