Abstract 3542: The Chemical Probes Portal: An essential resource providing expert advice on chemical tools for cancer research

Abstract

Abstract Background: The Chemical Probes Portal (Portal) serves as a vital resource in the realm of cancer research and biomedical science generally - offering expert guidance on high-quality chemical tools, usually protein inhibitors, crucial for studying physiological and pathological processes and validating therapeutic targets. Researchers often grapple with selecting suitable chemical probes, inadvertently utilizing tools ill-suited for their purpose, and not following best practice, thereby contaminating the scientific literature and wasting valuable time and resources. To address this challenge, the Portal (https://www.chemicalprobes.org) was established as a non-profit, independent online platform, meticulously curating, annotating, and scoring the quality of chemical probes and providing associated information and advice. Results: The Portal stands apart as the sole expert-curated public resource evaluating the quality and utility of small-molecule chemical tool compounds for use in cancer research and wider biomedical research. More than 250 experts, comprising scientific leaders in chemical biology, medicinal chemistry, pharmacology, and related fields, contribute their experience and insights to assess featured chemical probes. Since 2021, a progressively updated and enhanced version of the Portal has been operational, housing over 1000 compounds targeting 500+ proteins across diverse families, now including PROTACs and molecular glues. We also flag 254 ‘Unsuitables’, which are compounds that should not be used to interrogate a specific protein target. Additionally, the Portal now offers informative pages, providing advice delineating guidelines for selecting well-validated compounds, including those suitable for rodent studies, necessitating specific pharmacokinetic and pharmacodynamic properties. Best practice use requires employing high-quality chemical probes from more than one distinct chemical class that target the same protein, incorporating an inactive control compound, and following the recommended concentration range - all aimed at mitigating off-target risks. Conclusion: The enhanced Chemical Probes Portal provides a vital platform for researchers to navigate and evaluate chemical probes, easily and effectively. It employs a rigorous expert review to ensure the quality of the probes listed. The resource not only aids high-quality probe selection but also provides advice through an Information Centre, offering guidelines, FAQs, and additional information on probe criteria and use. The continuous expansion and outreach efforts aim to make the Portal an indispensable tool for cancer researchers and the broader biomedical research community. Researchers are encouraged to participate in the Portal's development and contribute to the robustness of chemical probe use in scientific endeavors. Citation Format: Domenico Sanfelice, Albert Antolin, Alisa Crisp, Yi Chen, Paul Brennan, Susanne Müller, Bissan Al-Lazikani, Aled Edwards, Paul Workman. The Chemical Probes Portal: An essential resource providing expert advice on chemical tools for cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3542.