Chemical probes are essential tools for exploring biological systems and validating drug targets. However, bioscientists need better information to avoid selection of out-of-date and flawed probes for their research.
The Chemical Probes Portal has been a valuable step forward through provision of expert curation and analysis. ICR researchers have now developed and made available a complementary web resource – Probe Miner – that enables the objective, large-scale analysis of chemical probes. Used together, these two resources equip researchers to make the best informed choices of chemical probe for biomedical research.
Key criteria for selecting chemical probes
In my previous blog post, ‘Call to bioscientists: choose and use your chemicaI probes very carefully’, I drew attention to the importance of critical assessment and selection of small molecule chemical probes (or tools) and their careful use for biological research and target validation.
In particular, I highlighted the continuing, inappropriate utilisation in biological research of out-of-date and often severely flawed compounds as chemical probes – resulting in pollution of the scientific literature with misleading information, wastage of researchers’ time and resources, and delays in the discovery of new medicines for the treatment of cancer and other diseases.
Visit the new chemical probes web resource – Probe Miner – released to the research community and led by Dr Bissan Al-Lazikani, Professor Paul Workman, Dr Albert Antolin and colleagues.
I also pointed out in the post the particularly important need to provide bioscience researchers, most especially those without detailed chemical biology and/or medicinal chemistry experience, with advice that equips them to select and use the best available chemical probes in their biomedical research.
In fact my blog post was centred on the recently published ‘Perspective’ in Cancer Cell that I co-wrote with my colleague Professor Julian Blagg with precisely that target audience in mind – bioscientists who wish to use chemical probes to explore fundamental biology or disease mechanisms. We mapped out the pitfalls and risks – illustrated by numerous case histories in cancer research.
We emphasized the key criteria that biologists should be aware of in selecting appropriate chemical probes for bioscience investigation and target validation. And we provided a set of do’s and don’ts, including the use of careful controls (ideally more than chemical of chemical inhibitor for each target and inactive control compounds; application of orthogonal biological tools; and inclusion of biomarkers to demonstrate target modulation by the selected chemical probes.
The importance of The Chemical Probes Portal
In the Perspective and the accompanying blog post we highlighted the importance of the The Chemical Probes Portal as an expert-curated resource for chemical probes. The establishment of the Portal as a community-driven wiki resource to improve quality and convey current best practice was discussed in a ‘Commentary’ article in Nature Chemical Biology. For full disclosure both Julian Blagg and myself are co-authors on that paper, we are both members of the Scientific Advisory Board of the Portal, and I am also a Board Director of the Portal.
The Chemical Probes Portal now has expert annotation and reports on over 400 chemical probes and is a growing influence among chemical biologists and we hope also the broader biomedical research field.
Notwithstanding the success of the Portal, a key missing capability for researchers – including both the expert chemical biology, medicinal chemistry and pharmacology aficionados and also the more general biology community that uses probes – has been the ability to utilise the vast volumes of public medicinal chemistry and chemical biology data to objectively assess at scale all available compounds for their suitability as chemical probes.
Probe Miner – a powerful, user-friendly resource
To address this need, my colleagues and I today release to the research community Probe Miner (probeminer.icr.ac.uk). Co-led by my ICR colleague Dr Bissan Al-Lazikani and myself, with the Wellcome Trust Research Fellow Albert Antolin performing the research implementation and important input from colleagues Ian Collins, Joe Tym and Angeliki Komianou, Probe Miner is a powerful, user-friendly web-based resource built on our computational and statistical analysis of >3.9 million experimental activities for >1.8million compounds in curated public medicinal chemistry databases.
Through Probe Miner we provide objective, data-driven systematic scoring of 355,305 compounds against 2,220 human targets. A description of the method and the resource is available on the bioRxiv pre-print server. The data and scores in Probe Miner are updated regularly based on new information in the underlying literature to ensure that researchers are armed with key information.
Employed in conjunction with the expert curation and advice from the Chemical Probes Portal – and also of course used in the context of the experience and knowledge of the individual scientist or team – Probe Miner enables the researchers to make informed choices in the selection of probes for their experiments.
We hope that both chemical probe experts and the general biomedical research community will find Probe Miner useful and we look forward to receiving feedback.
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