The identification of compounds that could be promising candidates for drug development has become easier following research by the Walter and Eliza Hall Institute's medicinal chemistry group.
Dr Jonathan Baell and Dr Georgina Holloway have developed a series of 'filters' that can be used to weed out those molecules likely to come up as false positives when screening a chemical library for compounds that could be useful in drug development.
High-throughput chemical screening (HTCS) seeks to identify chemical compounds that interact with a target protein and are therefore potential candidates for drug development. There can be from 30,000 to one million compounds in a screening library and thousands of compounds may be flagged as 'positive' for interaction with a protein of interest. These compounds then become the subject of time-consuming medicinal chemistry as scientists seek to refine them for entry into the drug development pipeline.
Dr Baell said about 10 per cent of compounds in any commercially available screening library might show up as false positives, potentially wasting hundreds of hours of scientists' time as they undertake labour-intensive medicinal chemistry to optimise these molecules.
"We're trying to remove molecules from the screening process that trick scientists into thinking they could be useful for being developed into drugs to treat disease but instead become a dead end," Dr Baell said.
To this end, Dr Baell and Dr Holloway analysed data from previous chemical screens and developed a way of clearly identifying those molecules likely to show up as false positives.
"These pan assay interference compounds, or PAINS as I like to call them, caused us some grief not so many years ago. For that reason, Georgina and I have taken some effort to identify these PAINS."
Dr Baell has made it possible for others to identify these troublesome molecules by developing 'filters', text fi
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Walter and Eliza Hall Institute