The Chemical Probes Portal: an enhanced public resource providing expert advice on chemical tools for cancer research

Background: Chemical probes, usually inhibitors, are essential tools to interrogate physiological and disease mechanisms validate drug targets. However, be useful, they must meet stringent criteria: evidence of potency, selectivity, cell permeability target engagement/modulation a ‘Pharmacological Audit Trail’. Unfortunately, researchers frequently rely on the historically biased literature or use search engines vendor catalogues, thus unwittingly selecting that may not fit-for-purpose outdated. This results in publication erroneous also incorrect decisions discovery, wasting substantial time resources. To help select best available tools, Probes Portal (CPP; www.chemicalprobes.org) was established 2015 as an independent, non-profit, online resource curate, annotate, score document quality chemical probes. Here, we describe its 2021 relaunch, enhancements usability content, future plans. Results: Since 2021, new enhanced version free, site is available, with >750 compounds, acting 390 targets across multiple protein families, featuring range including PROTACs molecular glues. Probe assessment based reviews by ∼200-member expert panel. The has faster, more intuitive easier forms for submitting/reviewing compounds. Reviewers now benefit from automated data input canSAR (cansarblack.icr.ac.uk), medchem, pharmacology biology plus other peer-reviewed sources. CPP links complementary Miner objective (probeminer.icr.ac.uk). features entirely database backend structure facilitate updates. We provide information pages, guidelines criteria choosing/using well-validated e.g., characterization probes animals, where suitable PK/PD properties needed. emphasize how practice includes ≥2 different classes (chemotypes) same well inactive control mitigating risk off-target effects. useful section ‘Historical Compounds’ which highlights those compounds have been superseded otherwise unsuitable Conclusion: invaluable community resource, enabling cancer choose their experiments. will continue expand toward proteome-wide coverage. extending our reach impact working journal editors, presentations at conferences, articles, blogs, webinars social media, collaborating closely Target 2035 initiative (www.target2035.net). Conflict interest: Ownership: DS, AC, EV-F, IM, YC, IC, PW, BA-L AAA are/were employees Institute Cancer Research (ICR), commercial interest ICR operates Rewards Inventors scheme whereby receive financial benefits following licensing project. AAA, PW instrumental creation/development and/or Miner. P.W. creation Portal. is/was consultant Darwin Health. employee MD Anderson Center Reward Scheme. declares Exscientia Astra Zeneca. consultant/ scientific advisory board member GSK, Open Targets, Astex Pharmaceuticals, Astellas Pharma ex-employee Inpharmatica Ltd. ChEMBL Director non-profit B.A.-L. consultant/scientific Pharma, Alterome Therapeutics, Black Diamond CV6 NextechInvest Ltd, Nuvectis Storm Therapeutics Vividion holds stock Alterome, Diamond, Chroma NextInvest, non-executive director executive former AstraZeneca. received research funding Astex, Cyclacel Merck KGaA, Nuvectis, Piramed Sixth Element Capital/CRT Pioneer Fund Vernalis. I.C. Epidarex LLP, AdoRx Enterprise Janssen Biopharma, Monte Rosa Fund. AG Sharp & Dohme.