4.Drug Target Identification

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Topics to be covered:
Typical Drug discovery Process
Advent of Molecular Biology
Microarray technology
Cellular Phenotyping
Disease Models
Pharmacogenomics/Personalised Medicine

Therapeutic Drug Discovery/Development Process
For the pharmaceutical industry, the discovery of a new drug presents an enormous scientific challenge
Drug discovery consists of the identification of new molecules or compounds, which act in new ways on biological targets specific to a disease.
Over the last 50 years, most of the drugs commercialized interact with only 500 known biological targets e.g.
Ion channels,
Signalling molecules (kinases),
Immune modulators,
Cytoskeleton proteins,
Enzymes,
Hormones,
Nuclear and cellular receptors etc.
However < 1% of the genome encodes all the proteins (and therefore all possible drug targets) potentially discoverable by the pharmaceutical industry for all time.

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Drug Screening using Cellular Phenotyping
Involves the use of vast numbers of cells that can be cultured quickly and tested in parallel for specific phenotypes.
Cellular phenotyping involves screening diseased cells using chemicals that could potentially convert them back to normal.
Allows analysis of the performance of specific types of proteins known to be defective in diseases.
e.g. Ion channels are a prime drug target which carry charged molecules back and forth across membranes and play key roles in diabetes and depression, heart disease, cystic fibrosis.
They are difficult to work with as they only function in membranes of living cells.
Ion channels can be assayed using fluorescent compounds which bind to membranes and fluoresce, or not, when a compound affects ion channel function.
Cells are placed in 1000s of separate wells on an assay plate. Fluorescent dyes are added and molecules are screened that can affect ion channel function.

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