About the Portal

The Chemical Probes Portal is a free, easily accessible online resource designed to help scientists in the biological and biomedical research communities to find and use high-quality small-molecule reagents called chemical probes for their laboratory studies. A unique feature of the Portal is that these tool molecules are evaluated by recognised chemical probe experts and recommendations are provided about how to best use them in experiments.

Chemical probes are powerful tools that are valuable across the entire bioscience research spectrum, ranging from fundamental biology studies through to translational health and disease research, and subsequent therapeutic development. Chemical probes can be inhibitors, activators or other modulators of protein function. For a further easy-to-read introduction we recommend this 'conversation' article.

The Chemical Probes Portal was established in 2015 (Arrowsmith et al, 2015 ) to help researchers manage the challenge of finding the needle they require within the massive internet-sized haystack of data. This is essential because the information necessary to select the best small molecule for experiments is scattered throughout the web and represents an overwhelming volume of diverse interdisciplinary data, of variable quality. The Chemical Probes Portal is designed to be user-friendly for biologists who lack chemical training, while still proving valuable to specialist chemical biologists and drug discovery scientists.

Of the online resources available to researchers (Antolin et al, 2021 ), the Chemical Probes Portal is unique in being the only one where the featured small-molecule compounds are evaluated by a large group (>260) of recognised chemical probe experts (the Scientific Expert Review Panel, or SERP). SERP members assess and rate the quality of chemical probes, guided by established criteria , providing comments and recommendations on how scientists can best utilise them in experimental systems – typically in in vitro cell and organ culture models but also, where appropriate, in experimental organisms, commonly mice. Reviewers rate probes on a scale of one to four stars for use in cell systems (with four stars denoting the highest quality) and may also provide a separate score for application in animal experiments. Probes awarded three to four stars are particularly recommended for use with confidence in experimental studies.

In addition to expert-curated chemical probe annotation and recommendations, the Portal has a wealth of information that can be useful to users of chemical probes, including the criteria that can be applied to assess them, general guidelines for use, and a range of other resources and FAQs .

Chemical probes are essential tools for elucidating the role of a given protein of interest (POI), including use in initial functional annotation and curiosity-driven biological discovery research, for example to elucidate the POI’s role in normal cell physiology. The availability of chemical tools has opened up many new areas of biology, as demonstrated by protein families such as nuclear hormone receptors, kinases and epigenetic regulators (Edwards et al 2011. The use of chemical probes is also commonly extended to translational research aimed at understanding the POI’s contribution to human health and disease, often leading to the identification and robust validation of protein targets in biomedical research, and subsequent multidisciplinary drug discovery (Bunnage et al, 2013; Garbaccio and Parmee, 2016 ).

The Portal currently focuses on human proteins but provides suggestions on how probes for studies in human systems can also be useful to interrogate proteins in other species or even across different biological kingdoms. See these examples in the fields of malaria parasite (Alam et al, 2019 ) and plant research (Auino et al 2017 ; Ercoli et al, 2022 ). Please also note that if the protein or probe that you are searching for is not included on the Portal then we provide advice on how you might proceed, including using alternative resources.

Chemical probes are highly complementary to genetic technologies for perturbing protein function and are synergistic when used alongside these as an orthogonal approach, thereby increasing the robustness of research findings (Weiss et al, 2007 ; Lin et al, 2019 ). Chemical probes offer several advantages, including their versatility for controlled concentration- and time-dependent protein perturbation, which facilitates the study of rapid onset of functional modulation and subsequent recovery from this. Additionally, their ease of use across a range of experimental biology setups is a significant benefit.

While the value of chemical probes is well-established, experience has shown that in order to provide reliable data in biological and biomedical research, chemical probes need to be well-characterized, demonstrated to be of high quality – especially exhibiting appropriate discrimination for the desired POI versus other proteins – and then used correctly (Workman and Collins, 2010 ; Frye, 2010 ; Arrowsmith et al, 2015 ; Sterling et al, 2023 ). Employing poor quality compounds, for example lacking sufficient selectivity, or using even high-quality probes inappropriately, particularly by omitting necessary probe controls or using too high a probe concentration, can produce misleading or incorrect results – thereby wasting time and resources. A Portal analysis has estimated that around $1.8 billion was lost in a single year owing to the use of unsuitable tool compounds.

The Portal now features over 1200 compounds with >1600 expert reviews covering >630 protein targets. More than 85% of the chemical probes are rated at the level of three or four stars. Criteria have been developed with Portal input (eg see Hartung et al, 2023 ) for different classes of small molecule tools, including conventional inhibitors, agonists, covalently acting agents, PROTACs (proteolysis targeting chimeras) and molecular glues. Our list of Unsuitable compounds, ie small-molecule reagents to be avoided when interrogating a specific POI, includes not only the most egregious nuisance compounds, such as the widely-used curcumin, resveratrol and staurosporine, but also small-molecule tools which have been useful in the past but are no longer considered ideal probes, often because they are superseded by those with greater selectivity.

The Portal is continuously enhancing as a resource, focusing especially on the continued increase in numbers and mechanistic diversity of new chemical probes and emphasizing wider coverage of the human proteome. Progress made by the Chemical Probes Portal has been described in publications in the database issues of Nucleic Acids Research (Antolin et al, 2023 ; Sanfelice et al, 2025 ).

Looking ahead, we will continue to work with our partners, including the Structural Genomics Consortium (SGC), Target 2035 and Donated Chemical Probes , together with our sister resources canSAR.ai and Probe Miner, to improve our own offering and interactivity – thereby enhancing ease of use and open access data-sharing, and supporting integration with a range of research software tools and other relevant resources. To allow maximum exploitation of the unique expert-led nature of our chemical probe annotation, we are further enhancing the Portal’s AI readiness to ensure that it can easily be used as a source of gold-standard FAIR data to support the increasingly important evaluation and development of AI and machine learning models.

To extend the impact of the Portal, we actively reach out to biological and biomedical scientists via a range of different mechanisms. This includes dissemination of knowledge and best practice through publications, conference presentations, and training and education events, including our popular Chemical Probe Hackathons for early career researchers, as well as via our social media channels.

To further develop a broader consensus on the selection and use of chemical probes across the wider bioscience community, we will work with partners and stakeholders to develop a widely applicable white paper – which journal editors tell us would be especially useful to them when reviewing papers submitted for publication. This will build on existing guidelines developed by the Portal, SGC and others.

In summary, chemical probes are transformative tools with broad applications across bioscience research, ranging from enabling fundamental biological and biomedical understanding all the way to applied translational research, including health intervention and therapeutic discovery – thus helping to bring about the downstream benefits to patients, the economy and society. The Chemical Probes Portal has become the frequently-used go-to resource to aid selection and use of these powerful small molecule tools, thereby increasing the rigour and reproducibility of research that is often limited by the quality of technical reagents (Prinz et al. 2011; Begley and Ellis, 2012; Baker, 2015).

By making it easier for scientists to identify and optimally utilize the best tools for their research, the Chemical Probes Portal fills a critical gap not only in supporting the expert chemical biology and drug discovery community but also by aiding the broader body of biological and biomedical researchers to generate robust and trustworthy data.

The Chemical Probes Portal is a community-led resource that is run for the benefit of the scientific community. We are grateful to all our supporters and encourage you to contact and join us.