Abstract A024: Probe Miner: objective, quantitative, data-driven assessment of chemical probes for target validation

Abstract

Abstract Chemical probes are important, widely used reagents for understanding biologic systems and for target validation. However, selection of chemical probes is largely subjective and prone to historical and commercial biases. Despite many publications discussing the aspirational properties of chemical probes and the proposal of "fitness factors" to be considered when assessing chemical tools, scientists often select probes through web-based searchers or previous literature that are heavily biased towards older and often flawed probes or use vendor catalogues that do not discriminate between probes. Here, we analyze the scope and quality of published bioactive molecules and uncover large biases and limitations of chemical tools in public databases that need to be urgently addressed and should be always considered when using chemical tools. We also provide the online Probe Miner resource (http://probeminer.icr.ac.uk) capitalizing on the plethora of public pharmacologic data to enable quantitative, unbiased, objective, Big Data-driven assessment of chemical probes and complement expert-curated approaches. We assess >1.8m compounds for their suitability as chemical tools against 2,220 human targets, demonstrating that large-scale public data can contribute to improving chemical probe assessment and prioritization to empower researchers in the selection of chemical tools for biomedical research and target validation. Citation Format: Albert A. Antolin, Joe E. Tym, Angeliki Komianou, Ian Collins, Paul Workman, Bissan Al-Lazikani. Probe Miner: objective, quantitative, data-driven assessment of chemical probes for target validation [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A024.