Resources
1) Chemical probes. A good chemical probe should be potent and selective. Many widely-used, commercially available probe molecules are not, or suffer from other limitations. Check the Chemical Probes Portal for information on targets and suitable chemical probes.
The promise and peril of chemical probes. Nat Chem Bio, 2015, 11, 536.
The art of the chemical probe. Nat Chem Bio, 2010, 6, 159.
2) High-throughput screening and PAINS compounds. Depending on the compound collection used, a high-throughput screening campaign may result in many false positive "hits". Series routinely reported as active against a variety of target classes have been labeled PAINS (pan-assay interference compounds), and described as "polluting the scientific literature". False positives may result from a variety of mechanisms including compound reactivity, redox-active molecules, and the ability to form aggregates under certain assay conditions. An awareness of these issues is essential for any screening efforts.
Chemical con artists foil drug discovery. Nature, 2014, 513, 481.
Learning from our mistakes: The 'unknown knowns' in fragment screening. Bioorg Med Chem Lett, 2013, 23, 2844.
Screening-based translation of public research encounters painful problems. ACS Med Chem Lett, 2015, 6, 229.
3) Academic drug discovery. Useful review discussing various issues in academic drug discovery:
Mitigating risk in academic preclinical drug discovery. Nat Rev Drug Disc, 2015, 14, 279.
The promise and peril of chemical probes. Nat Chem Bio, 2015, 11, 536.
The art of the chemical probe. Nat Chem Bio, 2010, 6, 159.
2) High-throughput screening and PAINS compounds. Depending on the compound collection used, a high-throughput screening campaign may result in many false positive "hits". Series routinely reported as active against a variety of target classes have been labeled PAINS (pan-assay interference compounds), and described as "polluting the scientific literature". False positives may result from a variety of mechanisms including compound reactivity, redox-active molecules, and the ability to form aggregates under certain assay conditions. An awareness of these issues is essential for any screening efforts.
Chemical con artists foil drug discovery. Nature, 2014, 513, 481.
Learning from our mistakes: The 'unknown knowns' in fragment screening. Bioorg Med Chem Lett, 2013, 23, 2844.
Screening-based translation of public research encounters painful problems. ACS Med Chem Lett, 2015, 6, 229.
3) Academic drug discovery. Useful review discussing various issues in academic drug discovery:
Mitigating risk in academic preclinical drug discovery. Nat Rev Drug Disc, 2015, 14, 279.