TY - JOUR
T1 - Objective, Quantitative, Data-Driven Assessment of Chemical Probes
AU - Antolin, Albert A.
AU - Tym, Joseph E.
AU - Komianou, Angeliki
AU - Collins, Ian
AU - Workman, Paul
AU - Al-Lazikani, Bissan
N1 - Funding Information:
This work was primarily supported through the People Program (Marie Curie Actions) of the 7th Framework Program of the European Union (FP7/2007-2013) under REA grant agreement no. 600388 (TECNIOspring program); the Agency of Business Competitiveness of the Government of Catalonia, ACCIÓ to A.A.A.; and the Wellcome Trust Sir Henry Wellcome Postdoctoral Fellowship ( 204735/Z/16/Z ) to A.A.A. The work utilizes the canSAR knowledge base, which is funded by a Cancer Research UK (CRUK) Strategic Project Award ( C35696/A23187 ) to B.A.-L. In addition, B.A.-L., I.C., and P.W. are funded by The Institute of Cancer Research (ICR) as well as the Cancer Research CRUK program grant to the Cancer Research UK Cancer Therapeutics Unit (grant C309/A11566 ). P.W is a CRUK Life Fellow. We acknowledge support from CRUK and NHS funding to the CRUK Centre and Biomedical Research Centre, respectively, at the ICR and Royal Marsden NHS Foundation Trust. The authors thank many collaborators for discussions and valuable input into the preparation of this manuscript. In particular, the authors thank Amy Donner for helpful discussion with regard to the Chemical Probes Portal and Gary Nugent for facilitating the chemoinformatics scripts to calculate the PAINS and the Level 1 scaffolds. We also thank early Probe Miner users for valuable feedback. A.A.A., J.E.T., A.K., I.C., P.W., and B.A.-L. are employees of The Institute of Cancer Research (ICR), which has a commercial interest in a range of drug targets. The ICR operates a Rewards to Inventors scheme through which employees of the ICR may receive financial benefit following commercial licensing of a project. P.W and I.C. are members of the Scientific Advisory Board of the non-profit Chemical Probes Portal and P.W. is also a Board Director.
Publisher Copyright:
© 2017 The Authors
PY - 2018/2/15
Y1 - 2018/2/15
N2 - Chemical probes are essential tools for understanding biological systems and for target validation, yet selecting probes for biomedical research is rarely based on objective assessment of all potential compounds. Here, we describe the Probe Miner: Chemical Probes Objective Assessment resource, capitalizing on the plethora of public medicinal chemistry data to empower quantitative, objective, data-driven evaluation of chemical probes. We assess >1.8 million compounds for their suitability as chemical tools against 2,220 human targets and dissect the biases and limitations encountered. Probe Miner represents a valuable resource to aid the identification of potential chemical probes, particularly when used alongside expert curation. Chemical probe selection remains largely subjective, not utilizing extensive medicinal chemistry data, causing widespread use of flawed probes. Antolin et al. describe the Probe Miner resource, empowering objective, quantitative, data-driven assessment of chemical probes based on regularly updated large-scale data.
AB - Chemical probes are essential tools for understanding biological systems and for target validation, yet selecting probes for biomedical research is rarely based on objective assessment of all potential compounds. Here, we describe the Probe Miner: Chemical Probes Objective Assessment resource, capitalizing on the plethora of public medicinal chemistry data to empower quantitative, objective, data-driven evaluation of chemical probes. We assess >1.8 million compounds for their suitability as chemical tools against 2,220 human targets and dissect the biases and limitations encountered. Probe Miner represents a valuable resource to aid the identification of potential chemical probes, particularly when used alongside expert curation. Chemical probe selection remains largely subjective, not utilizing extensive medicinal chemistry data, causing widespread use of flawed probes. Antolin et al. describe the Probe Miner resource, empowering objective, quantitative, data-driven assessment of chemical probes based on regularly updated large-scale data.
KW - chemical probes
KW - chemical tools
KW - large-scale
KW - objective quantitative assessment
KW - online public resource
KW - target validation
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U2 - 10.1016/j.chembiol.2017.11.004
DO - 10.1016/j.chembiol.2017.11.004
M3 - Article
C2 - 29249694
AN - SCOPUS:85039435630
SN - 2451-9456
VL - 25
SP - 194-205.e5
JO - Cell Chemical Biology
JF - Cell Chemical Biology
IS - 2
ER -