Erratum: Choose and Use Your Chemical Probe Wisely to Explore Cancer Biology (Cancer Cell (2017) 32(1) (9–25) (S1535610817302556) (10.1016/j.ccell.2017.06.005));Choose and Use Your Chemical Probe Wisely to Explore Cancer Biology

Cancer Cell

Volumn 32, Issue 1, 2017, Pages 9-25

  Blagg, Julian ^a   Workman, Paul ^a  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

Author keywords

biochemical selectivity; chemical probe; chemical reactivity; chemical tool; ligand promiscuity; lipophilicity; PAINS; Pan Assay Interference Compounds; pharmacological audit trail; pharmacophore crossing; target validation

Indexed keywords

BIOLOGICAL PRODUCT; BRM PROTEIN; HEAT SHOCK PROTEIN 70; HISTONE; HISTONE DEMETHYLASE; HYPOXIA INDUCIBLE FACTOR 2ALPHA; IMMUNOGLOBULIN F(AB) FRAGMENT; INIPARIB; K RAS PROTEIN; LIGAND; MCB 613; REAGENT; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; MOLECULAR PROBE;

AUTOPHAGY; HUMAN; LIPOPHILICITY; MALIGNANT NEOPLASM; MOLECULARLY TARGETED THERAPY; PHARMACOPHORE; PRIORITY JOURNAL; PROTEIN AGGREGATION; REVIEW; CHEMISTRY; METABOLISM; METHODOLOGY; MOLECULAR PROBE; NEOPLASM; PATHOLOGY; PATHOPHYSIOLOGY; STANDARDS;

HUMANS; MOLECULAR PROBES; NEOPLASMS; RESEARCH DESIGN;

EID: 85027456680     PISSN: 15356108     EISSN: 18783686     Source Type: Journal    
DOI: 10.1016/j.ccell.2017.07.010     Document Type: Erratum

References (131)

1. American Association for Cancer Research. (2015). Proceedings: AACR 106th Annual Meeting 2015. Philadelphia. Cancer Res. 75, 15 Supplement.
2. American Association for Cancer Research. (2017). CICR: general resources. Resources for understanding the proper use of chemical tools in cancer research. http://www.aacr.org/MEMBERSHIP/PAGES/SCIENTIFIC%20WORKING%20GROUPS/CICR-GENERAL-RESOURCES.ASPX#.WKTFQ_4SHbi. Accessed March 16, 2017.
3. Arrowsmith, C.H., Audia, J.E., Austin, C., Baell, J., Bennett, J., Blagg, J., Bountra, C., Brennan, P.E., Brown, P.J., Bunnage, M.E., et al. The promise and peril of chemical probes. Nat. Chem. Biol. 11 (2015), 536–541.
4. Ashworth, A., A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J. Clin. Oncol. 26 (2008), 3785–3790.
5. Baell, J.B., Holloway, G.A., New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J. Med. Chem. 53 (2010), 2719–2740.
6. Baell, J., Walters, M.A., Chemical con artists foil drug discovery. Nature 513 (2014), 481–483.
7. Baker, M., Fragment-based lead discovery grows up. Nat. Rev. Drug Discov. 12 (2013), 5–7.
8. Banerji, U., Workman, P., Critical parameters in targeted drug development: the pharmacological audit trail. Semin. Oncol. 43 (2016), 436–445.
9. Barelier, S., Sterling, T., O'Meara, M.J., Shoichet, B.K., The recognition of identical ligands by unrelated proteins. ACS Chem. Biol. 10 (2015), 2772–2784.
10. Baud, M.G., Lin-Shiao, E., Cardote, T., Tallant, C., Pschibul, A., Chan, K.H., Zengerle, M., Garcia, J.R., Kwan, T.T., Ferguson, F.M., Ciulli, A., A bump-and-hole approach to engineer controlled selectivity of BET bromodomain chemical probes. Science 346 (2014), 638–641.
11. Begley, C.G., Ellis, L.M., Drug development: raise standards for preclinical cancer research. Nature 483 (2012), 531–533.
12. Bishop, A.C., Ubersax, J.A., Petsch, D.T., Matheos, D.P., Gray, N.S., Blethrow, J., Shimizu, E., Tsien, J.Z., Schultz, P.G., Rose, M.D., et al. A chemical switch for inhibitor-sensitive alleles of any protein kinase. Nature 407 (2000), 395–401.
13. Blagg, J., Structure-activity relationships for in vitro and in vivo toxicity. Annu. Rep. Med. Chem. 41 (2006), 353–368.
14. Blagg, J., Structural alerts for toxicity. Abraham, D.J., Rotella, D.P., (eds.) Burger's Medicinal Chemistry and Drug Discovery, 2010, Wiley, 301–334.
15. Blagg, J., Workman, P., Chemical biology approaches to target validation in cancer. Curr. Opin. Pharmacol. 17 (2014), 87–100.
16. Blevitt, J.M., Hack, M.D., Herman, K.L., Jackson, P.F., Krawczuk, P.J., Lebsack, A.D., Liu, A.X., Mirzadegan, T., Nelen, M.I., Patrick, A.N., et al. Structural basis of small-molecule aggregate induced inhibition of a protein–protein interaction. J. Med. Chem. 60 (2017), 3511–3517.
17. Blum, L.C., Reymond, J.L., 970 million druglike small molecules for virtual screening in the chemical universe database GDB-13. J. Am. Chem. Soc. 131 (2009), 8732–8733.
18. Bondeson, D.P., Mares, A., Smith, I.E.D., Ko, E., Campos, S., Miah, A.H., Mulholland, K.E., Routly, N., Buckley, D.L., Gustafson, J.L., et al. Catalytic in vivo protein knockdown by small molecule PROTACs. Nat. Chem. Biol. 11 (2015), 611–617.
19. Bordeaux, J., Welsh, A.K., Agarwal, S., Killiam, E., Baquero, M.T., Hanna, J.A., Anagnostou, V.K., Rimm, D.L., Antibody validation. BioTechniques 48 (2010), 197–209.
20. Bottcher, T., An additive definition of molecular complexity. J. Chem. Inf. Model. 56 (2016), 462–470.
21. Bowes, J., Brown, A.J., Hamon, J., Jarolimek, W., Sridhar, A., Waldron, G., Whitebread, S., Reducing safety-related drug attrition: the use of in vitro pharmacological profiling. Nat. Rev. Drug Discov. 11 (2012), 909–922.
22. Bruns, R.F., Wilson, I.A., Rules for identifying potentially reactive or promiscuous compounds. J. Med. Chem. 55 (2012), 9763–9772.
23. Bunnage, M.E., Chekler, E.L., Jones, L.H., Target validation using chemical probes. Nat. Chem. Biol. 9 (2013), 195–199.
24. Cancer Cell Line Encyclopedia Consortium, The Genomics of Drug Sensitivity in Cancer Consortium. Pharmacogenomic agreement between two cancer cell line data sets. Nature 528 (2015), 84–87.
25. Capuzzi, S.J., Muratov, E.N., Tropsha, A., Phantom PAINS: problems with the utility of alerts for pan-assay interference compounds. J. Chem. Inf. Model. 57 (2017), 417–427.
26. Chakraborty, M., Joo Jin, K., Glover, S.A., Novak, M., Characterization of the 4-(Benzothiazol-2-yl)phenylnitrenium ion from a putative metabolite of a model antitumor drug. J. Org. Chem. 75 (2010), 5296–5304.
27. Chemical Probes Portal. (2017a). Portal News: Rigorous evaluation of chemical probes advances drug discovery efforts. http://us12.campaign-archive2.com/?u=26d744443f0b394b8c0a3ba6d&id=9c39807005#mctoc1. Accessed March 16, 2017.
28. Chemical Probes Portal. (2017b). Historic Compounds. http://www.chemicalprobes.org/historic-compounds. Accessed March 16, 2017.
29. Chemical Probes Portal. (2017c). Homepage. http://www.chemicalprobes.org. Accessed March 16, 2017.
30. Cho, H., Du, X., Rizzi, J.P., Liberzon, E., Chakraborty, A.A., Gao, W., Carvo, I., Signoretti, S., Bruick, R.K., Josey, J.A., et al. On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models. Nature 539 (2016), 107–111.
31. Ciceri, P., Müller, S., O'Mahony, A., Fedorov, O., Filippakopoulos, P., Hunt, J.P., Lasater, E.A., Pallares, G., Picaud, S., Wells, C., et al. Dual kinase-bromodomain inhibitors for rationally designed polypharmacology. Nat. Chem. Biol. 10 (2014), 305–312.
32. Collins, F.S., Tabak, L.A., Policy: NIH plans to enhance reproducibility. Nature 505 (2014), 612–613.
33. Curpăn, R., Avram, S., Vianello, R., Bologa, C., Exploring the biological promiscuity of high-throughput screening hits through DFT calculations. Bioorg. Med. Chem. 22 (2014), 2461–2468.
34. Dale, T., Clarke, P.A., Esdar, C., Waalboer, D., Adeniji-Popoola, O., Ortiz-Ruiz, M., Mallinger, A., Samant, R.S., Czodrowski, P., Musil, D., et al. Identification of a potent and selective chemical probe for exploring the role of Mediator complex-associated protein kinases CDK8 and CDK19 in human disease. Nat. Chem. Biol. 11 (2015), 973–980.
35. de Haard, H.J., van Neer, N., Reurs, A., Hufton, S.E., Roovers, R.C., Henderikx, P., de Bruïne, A.P., Arends, J.-W., Hoogenboom, H.R., A large non-immunized human fab fragment phage library that permits rapid isolation and kinetic analysis of high affinity antibodies. J. Biol. Chem. 274 (1999), 18218–18230.
36. Dittmann, A., Werner, T., Chung, C.-W., Savitski, M.M., Fälth Savitski, M., Grandi, P., Hopf, C., Lindon, M., Neubauer, G., Prinjha, R.K., et al. The commonly used PI3-kinase probe LY294002 is an inhibitor of BET bromodomains. ACS Chem. Biol. 9 (2014), 495–502.
37. Doudna, J.A., Charpentier, E., The new frontier of genome engineering with CRISPR-Cas9. Science, 346, 2014, 1258096.
38. Ember, S.W.J., Zhu, J.-Y., Olesen, S.H., Martin, M.P., Becker, A., Berndt, N., Georg, G.I., Schonbrunn, E., Acetyl-lysine binding site of bromodomain-containing protein 4 (BRD4) interacts with diverse kinase inhibitors. ACS Chem. Biol. 9 (2014), 1160–1171.
39. Eng, C.H., Wang, Z., Tkach, D., Toral-Barza, L., Ugwonali, S., Liu, S., Fitzgerald, S.L., George, E., Frias, E., Cochran, N., et al. Macroautophagy is dispensable for growth of KRAS mutant tumors and chloroquine efficacy. Proc. Natl. Acad. Sci. USA 113 (2016), 182–187.
40. Engel, J., Lategahn, J., Rauh, D., Hope and disappointment: covalent inhibitors to overcome drug resistance in non-small cell lung cancer. ACS Med. Chem. Lett. 7 (2015), 2–5.
41. Enthammer, M., Papadakis, E.S., Gachet, M.S., Deutsch, M., Schwaiger, S., Koziel, K., Ashraf, M.I., Khalid, S., Wolber, G., Packham, G., et al. Isolation of a novel thioflavin s–derived compound that inhibits bag-1–mediated protein interactions and targets BRAF inhibitor–resistant cell lines. Mol. Cancer Ther. 12 (2013), 2400–2414.
42. Eurofins/CEREP. (2017). Standard profiles. http://www.cerep.fr/cerep/users/pages/catalog/profiles/catalog.asp. Accessed March 16, 2017.
43. European Monoclonal Antibodies Network. (2017). EuroMabNet: European monoclonal antibodies network. https://www.euromabnet.com/. Accessed May 16, 2017.
44. Evans, L.E., Cheeseman, M.D., Yahya, N., Jones, K., Investigating apoptozole as a chemical probe for HSP70 inhibition. PLoS One, 10, 2015, e0140006.
45. Extance, A. (2015). Pfizer's Response to Compound Fraud Spotlights Quality Issues. RSC Chemistry World, 7th December 2015.
46. Filippakopoulos, P., Knapp, S., Targeting bromodomains: epigenetic readers of lysine acetylation. Nat. Rev. Drug Discov. 13 (2014), 337–356.
47. Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W.B., Fedorov, O., Morse, E.M., Keates, T., Hickman, T.T., Felletar, I., et al. Selective inhibition of BET bromodomains. Nature 468 (2010), 1067–1073.
48. Finlay, M.R., Anderton, M., Ashton, S., Ballard, P., Bethel, P.A., Box, M.R., Bradbury, R.H., Brown, S.J., Butterworth, S., Campbell, A., et al. Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptor. J. Med. Chem. 57 (2014), 8249–8267.
49. Fischer, E.S., Bohm, K., Lydeard, J.R., Yang, H., Stadler, M.B., Cavadini, S., Nagel, J., Serluca, F., Acker, V., Lingaraju, G.M., et al. Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide. Nature 512 (2014), 49–53.
50. Frearson, J., Wyatt, P., Drug discovery in academia: the third way. Expert Opin. Drug Discov. 5 (2010), 909–919.
51. Frye, S.V., The art of the chemical probe. Nat. Chem. Biol. 6 (2010), 159–161.
52. Frye, S., Crosby, M., Edwards, T., Juliano, R., US Academic drug discovery. Nat. Rev. Drug Discov. 10 (2011), 409–410.
53. Frye, S.V., Arkin, M.R., Arrowsmith, C.H., Conn, P.J., Glicksman, M.A., Hull-Ryde, E.A., Slusher, B.S., Tackling reproducibility in academic preclinical drug discovery. Nat. Rev. Drug Discov. 14 (2015), 733–734.
54. Fu, Y., Sander, J., Reyon, D., Cascio, V.M., Joung, J.K., Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat. Biotechnol. 32 (2014), 279–284.
55. Garbaccio, R.M., Parnee, E.R., The impact of chemical probes in drug discovery: a pharmaceutical industry perspective. Cell Chem. Biol. 23 (2016), 10–17.
56. Gleeson, M.P., Hersey, A., Montanari, D., Overington, J., Probing the links between in vitro potency, ADMET and physicochemical parameters. Nat. Rev. Drug Discov. 10 (2011), 197–208.
57. Griffith, M., Griffith, O.L., Coffman, A.C., Weible, J.V., McMichael, J.F., Spies, N.C., Koval, J., Das, I., Callaway, M.B., Eldred, J.M., et al. DGIdb: mining the druggable genome. Nat. Methods 10 (2013), 1209–1210.
58. Hall, J., Unravelling the general properties of siRNAs: strength in numbers and lessons from the past. Nat. Genet. 5 (2004), 552–557.
59. Hall, R.J., Mortenson, P.N., Murray, C.W., Efficient exploration of chemical space by fragment-based screening. Prog. Biophys. Mol. Biol. 116 (2014), 82–91.
60. Hancox, J.C., McPate, M.J., El Harchi, A., Zhang, Y.H., The hERG potassium channel and hERG screening for drug-induced torsades de pointes. Pharmacol. Ther. 119 (2008), 118–132.
61. Hann, M.M., Keserü G.M., Finding the sweet spot: the role of nature and nurture in medicinal chemistry. Nat. Rev. Drug Discov. 11 (2012), 355–365.
62. Hann, M.M., Leach, A.R., Harper, G., Molecular complexity and its impact on the probability of finding leads for drug discovery. J. Chem. Inf. Model. 41 (2001), 856–864.
63. Højfeldt, J.W., Agger, K., Helin, K., Histone lysine demethylases as targets for anticancer therapy. Nat. Rev. Drug Discov. 12 (2014), 917–930.
64. Hopkins, A.L., Groom, C.R., The druggable genome. Nat. Rev. Drug Discov. 1 (2002), 727–730.
65. Huber, K.V.M., Target engagement: shining a light. Nat. Chem. Biol. 13 (2017), 133–134.
66. Irwin, J.J., Duan, D., Torosyan, H., Doak, A.K., Ziebart, K.T., Sterling, T., Tumanian, G., Shoichet, B.K., An aggregation advisor for ligand discovery. J. Med. Chem. 58 (2015), 7076–7087.
67. Janzen, W.P., Screening technologies for small molecule discovery: the state of the art. Chem. Biol. 21 (2014), 1162–1170.
68. Jones, A.M., Westwood, I.M., Osborne, J.D., Matthews, T.P., Cheeseman, M.D., Rowlands, M.G., Jeganathan, F., Burke, R., Lee, D., Kadi, N., et al. A fragment-based approach applied to a highly flexible target: insights and challenges towards the inhibition of HSP70 isoforms. Sci. Rep., 6, 2016, 34701.
69. Kaelin, W.G., Common pitfalls in preclinical cancer target validation. Nat. Rev. Cancer, 2017, 10.1038/nrc.2017.32.
70. Kato, M., Hammam, M.A.S., Taniguchi, T., Suga, Y., Monde, K., What is the true structure of D609, a widely used lipid related enzyme inhibitor?. Org. Lett. 18 (2016), 768–771.
71. Kawamura, T., Kawatani, M., Muroi, M., Kondoh, Y., Futamura, Y., Aono, H., Tanaka, M., Honda, K., Osada, H., Proteomic profiling of small-molecule inhibitors reveals dispensability of MTH1 for cancer survival. Sci. Rep., 6, 2016, 26521.
72. Kasap, C., Elemento, O., Kapoor, T.M., DrugTargetSeqR: a genomics- and CRISPR-Cas9–based method to analyze drug targets. Nat. Chem. Biol. 10 (2014), 626–628.
73. Kettle, J.G., Alwan, H., Bista, M., Breed, J., Davies, N.L., Eckersley, K., Fillery, S., Foote, K.M., Goodwin, L., Jones, D.R., et al. Potent and selective inhibitors of MTH1 probe its role in cancer cell survival. J. Med. Chem. 59 (2016), 2346–2361.
74. Klaeger, S., Gohlke, B., Perrin, J., Gupta, V., Heinzlmeir, S., Helm, D., Qiao, H., Bergamini, G., Handa, H., Savitski, M.M., et al. Chemical proteomics reveals ferrochelatase as a common off-target of kinase inhibitors. ACS Chem. Biol. 11 (2016), 1245–1254.
75. Komarov, P.G., Komarova, E.A., Kondratov, R.V., Christov-Tselkov, K., Coon, J.S., Chernov, M.V., Gudkov, A.V., A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science 285 (1999), 1733–1737.
76. Kruidenier, L., Chung, C.-W., Cheng, Z., Liddle, J., Che, K., Joberty, G., Bantscheff, M., Bountra, C., Bridges, A., Diallo, H., et al. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature 488 (2012), 404–408.
77. Lamb, J., Crawford, E.D., Peck, D., Modell, J.W., Blat, I.C., Wrobel, M.J., Lerner, J., Brunet, J.-P., Subramanian, A., Ross, K.N., et al. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science 313 (2006), 1929–1935.
78. Lanning, B.R., Whitby, L.R., Dix, M.M., Douhan, J., Gilbert, A.M., Hett, E.C., Johnson, T.O., Joslyn, C., Kath, J.C., Niessen, S., et al. A road map to evaluate the proteome-wide selectivity of covalent kinase inhibitors. Nat. Chem. Biol. 10 (2014), 760–767.
79. Lauer, M. (2016). Authentication of key biological and/or chemical resources in NIH grant applications. Open Mike. https://nexus.od.nih.gov/all/2016/01/29/authentication-of-key-biological-andor-chemical-resources-in-nih-grant-applications. Accessed May 13, 2017.
80. Leach, A.R., Hann, M.M., Molecular complexity and fragment-based drug discovery: ten years on. Curr. Opin. Chem. Biol. 15 (2011), 489–496.
81. Leeson, P.D., Springthorpe, B., The influence of drug-like concepts on decision making in medicinal chemistry. Nat. Rev. Drug Discov. 6 (2007), 881–890.
82. Lin, A., Giuliano, C.J., Sayles, N.M., Sheltzer, J.M., CRISPR/Cas9 mutagenesis invalidates a putative cancer dependency targeted in on-going clinical trials. Elife, 6, 2017 e24179.
83. Liu, X., Shi, Y., Maag, D.X., Palma, J.P., Patterson, M.J., Ellis, P.A., Surber, B.W., Ready, D.B., Soni, N.B., Ladror, U.S., et al. Iniparib nonselectively modifies cysteine-containing proteins in tumor cells and is not a bona fide PARP inhibitor. Clin. Cancer Res. 18 (2012), 510–523.
84. Liu, Q., Sabnis, Y., Zhao, Z., Zhang, T., Buhrlage, S.J., Jones, L.H., Gray, N.S., Developing irreversible inhibitors of the protein kinase cysteinome. Chem. Biol. 20 (2013), 146–159.
85. Lounkine, E., Keiser, M.J., Whitebread, S., Mikhailov, D., Hamon, J., Jenkins, J.L., Lavan, P., Weber, E., Doak, A.K., Cote, S., et al. Large-scale prediction and testing of drug activity on side-effect targets. Nature 486 (2012), 361–367.
86. Lowe, D. (2016). In the pipeline. What does one do with these? http://blogs.sciencemag.org/pipeline/archives/2016/01/19/what-does-one-do-with-these.
87. Lowe, D. (2017). In the pipeline. No easy road to getting rid of PAINS. http://blogs.sciencemag.org/pipeline/archives/2017/02/07/no-easy-road-to-getting-rid-of-pains.
88. McAllister, T.E., England, K.S., Hopkinson, R.J., Brennan, P.E., Kawamura, A., Schofield, C.J., Recent progress in histone demethylase inhibitors. J. Med. Chem. 59 (2016), 1308–1329.
89. McGovern, S.L., Helfand, B.T., Feng, B., Shoichet, B.K., A specific mechanism of nonspecific inhibition. J. Med. Chem. 46 (2003), 4265–4272.
90. Muroi, M., Sayaka Kazami, S., Noda, K., Kondo, H., Takayama, H., Kawatani, M., Usui, T., Osada, H., Application of proteomic profiling based on 2D-DIGE for classification of compounds according to the mechanism of action. Chem. Biol. 17 (2010), 460–470.
91. National Cancer Institute. (2017). Office of Cancer Clinical Proteomics Research Antibody Portal. https://antibodies.cancer.gov/apps/site/default. Accessed March 16, 2017.
92. Ndubaku, C.O., Crawford, J.J., Drobnick, J., Aliagas, I., Campbell, D., Dong, P., Dornan, L.M., Duron, S., Epler, J., Gazzard, L., et al. Design of selective PAK1 inhibitor G-5555: improving properties by employing an unorthodox low-pKa polar moiety. ACS Med. Chem. Lett. 6 (2015), 1241–1246.
93. Nicodeme, E., Jeffrey, K.L., Schaefer, U., Beinke, S., Dewell, S., Chung, C.-W., Chandwani, R., Marazzi, I., Wilson, P., Coste, H., et al. Suppression of inflammation by a synthetic histone mimic. Nature 468 (2010), 1119–1123.
94. Oprea, T.I., Bologa, C.G., Boyer, S., Curpan, R.F., Glen, R.C., Hopkins, A.L., Lipinski, C.A., Marshall, G.R., Martin, Y.C., Ostopovici-Halip, L., et al. A crowdsourcing evaluation of the NIH chemical probes. Nat. Chem. Biol. 5 (2009), 441–447.
95. Ortiz Torres, I., Kuchenbecker, K.M., Nnadi, C.I., Fletterick, R.J., Kelly, M.J., Fujimori, D.G., Histone demethylase KDM5A is regulated by its reader domain through a positive-feedback mechanism. Nat. Commun., 6, 2015, 6204.
96. Overington, J.P., Al-Lazikani, B., Hopkins, A.L., How many drug targets are there?. Nat. Rev. Drug Discov. 5 (2006), 993–996.
97. Parker, C.G., Galmozzi, A., Wang, Y., Correia, B.E., Sasaki, K., Joslyn, C.M., Kim, A.S., Cavallaro, C.L., Lawrence, R.M., Johnson, S.R., et al. Ligand and target discovery by fragment-based screening in human cells. Cell 168 (2017), 527–541.
98. Patel, A.G., De Lorenzo, S.B., Flatten, K.S., Poirier, G.G., Kaufmann, S.H., Failure of iniparib to inhibit poly(ADP-ribose) polymerase in vitro. Clin. Cancer Res. 18 (2012), 1655–1662.
99. Persengiev, S.P., Zhu, X., Green, M.R., Nonspecific, concentration-dependent stimulation and repression of mammalian gene expression by small interfering RNAs (siRNAs). RNA 10 (2004), 12–18.
100. Peters, J.U., Schnider, P., Mattei, P., Kansy, M., Pharmacological promiscuity: dependence on compound properties and target specificity in a set of recent Roche compounds. ChemMedChem 4 (2009), 680–686.
101. Polier, S., Samant, R.S., Clarke, P.A., Workman, P., Prodromou, C., Pearl, L.H., ATP-competitive inhibitors block protein kinase recruitment to the Hsp90-Cdc37 system. Nat. Chem. Biol. 9 (2013), 307–312.
102. Ponten, F., Jirstrom, K., Uhlen, M., The human protein Atlas — a tool for pathology. J. Pathol. 216 (2008), 387–393.
103. Powers, M.V., Jones, K., Barillari, C., Westwood, I., van Montford, R.L.M., Workman, P., Targeting HSP70: the second potentially druggable heat shock protein and molecular chaperone?. Cell Cycle 9 (2010), 1542–1550.
104. Prinz, F., Schlange, T., Asadullah, K., Believe it or not: how much can we rely on published data on potential drug targets?. Nat. Rev. Drug Discov., 10, 2011, 712.
105. Roncador, G., Engel, P., Maestre, L., Anderson, A.P., Cordell, J.L., Cragg, M.S., Serbec, V.C., Jones, M., Lisnic, V.J., Kremer, L., et al. The European antibody network's practical guide to finding and validating suitable antibodies for research. MAbs 8 (2016), 27–36.
106. Rothman, R.B., Baumann, M.H., Savage, J.E., Rauser, L., McBride, A., Hufeisen, S.J., Roth, B.L., Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation 102 (2000), 2836–2841.
107. Santos, R., Ursu, O., Gaulton, A., Bento, A.P., Donadi, R.S., Bologa, C.G., Karlsson, A., Al-Lazikani, B., Hersey, A., Oprea, T.I., et al. A comprehensive map of molecular drug targets. Nat. Rev. Drug Discov. 16 (2017), 19–34.
108. Schenone, M., Dančík, V., Wagner, B.K., Clemons, P.A., Target identification and mechanism of action in chemical biology and drug discovery. Nat. Chem. Biol. 9 (2013), 232–240.
109. Seashore-Ludlow, B., Rees, M.G., Cheah, J.H., Cokol, M., Price, E.V., Coletti, M.E., Jones, V., Bodycombe, N.E., Soule, C.K., Gould, J., et al. Harnessing connectivity in a large-scale small-molecule sensitivity dataset. Cancer Discov. 5 (2015), 1210–1223.
110. Sells, T.B., Chau, R., Ecsedy, J.A., Gershman, R.E., Hoar, K., Huck, J., Janowick, D.A., Kadambi, V.J., LeRoy, P.J., Stirling, M., et al. MLN8054 and alisertib (MLN8237): discovery of selective oral aurora a inhibitors. ACS Med. Chem. Lett. 6 (2015), 630–634.
111. Sharp, A., Crabb, S.J., Johnson, P.W., Hague, A., Cutress, R., Townsend, P.A., Ganesan, A., Packham, G., Thioflavin S (NSC71948) interferes with Bcl-2-associated athanogene (BAG-1)-mediated protein-protein interactions. J. Pharmacol. Exp. Ther. 331 (2009), 680–689.
112. Simon, G.M., Niphakis, M.J., Cravatt, B.F., Determining target engagement in living systems. Nat. Chem. Biol. 9 (2013), 200–205.
113. Sinja, G., Downfall of iniparib: a PARP inhibitor that doesn't inhibit PARP after all. J. Natl. Cancer Inst., 106, 2014, djt447.
114. Steele, A.J., Prentice, A.G., Hoffbrand, A.V., Yogashangary, B.C., Hart, S.M., Lowdell, M.W., Samuel, E.R., North, J.M., Nacheva, E.P., Chanalaris, A., et al. 2-Phenylacetylenesulfonamide (PAS) induces p53-independent apoptotic killing of B-chronic lymphocytic leukemia (CLL) cells. Blood 114 (2009), 1217–1225.
115. Strom, E., Sathe, S., Komarov, P.G., Chernova, O.B., Pavlovska, I., Shyshynova, I., Bosykh, D.A., Burdelya, L.G., Macklis, R.M., Skaliter, R., et al. Small-molecule inhibitor of p53 binding to mitochondria protects mice from gamma radiation. Nat. Chem. Biol. 2 (2006), 474–479.
116. Structural Genomics Consortium (2011). Cerep to build epigenetics screening and profiling laboratory in Toronto. http://www.thesgc.org/news/SGC_Cerep_PR_June13. Accessed March 16, 2017.
117. Structural Genomics Consortium (2017). GSK-LSD1 A chemical probe for LSD1. http://www.thesgc.org/chemical-probes/GSK-LSD1. Accessed March 17, 2017.
118. Su, Z., Wang, F., Lee, J.H., Stephens, K.E., Papazyan, R., Voronina, E., Krautkramer, K.A., Raman, A., Thorpe, J.J., Boersma, M.D., et al. Reader domain specificity and lysine demethylase-4 family function. Nat. Commun., 7, 2016, 13387.
119. Sushko, I., Salmina, E., Potemkin, V.A., Poda, G., Tetko, I.V., ToxAlerts: a web server of structural alerts for toxic chemicals and compounds with potential adverse reactions. J. Chem. Inf. Model. 52 (2012), 2310–2316.
120. Swinney, D.C., Anthony, J., How were new medicines discovered?. Nat. Rev. Drug Discov. 10 (2011), 507–519.
121. Tarcsay, Á., Keserű G.M., Contributions of molecular properties to drug promiscuity. J. Med. Chem. 56 (2013), 1789–1795.
122. Uhlen, M., Bandrowski, A., Carr, S., Edwards, A., Ellenberg, J., Lundberg, E., Rimm, D.L., Rodriguez, H., Hiltke, T., Snyder, M., Yamamoto, T., A proposal for validation of antibodies. Nat Methods 13 (2016), 823–827.
123. Vangamudi, B., Paul, T.A., Shah, P.K., Kost-Alimova, M., Nottebaum, L., Shi, X., Zhan, Y., Leo, E., Mahadeshwar, H.S., Protopopov, A., et al. The SMARCA2/4 ATPase domain surpasses the bromodomain as a drug target in SWI/SNF-mutant cancers: insights from cDNA rescue and PFI-3 inhibitor studies. Cancer Res. 75 (2015), 3865–3878.
124. Walton, S.P., Stephanopoulos, G.N., Yarmush, M.L., Roth, C.M., Thermodynamic and kinetic characterization of antisense oligodeoxynucleotide binding to a structured mRNA. Biophys. J. 82 (2001), 366–377.
125. Walton, M.I., Wilson, S.C., Hardcastle, I.R., Mirza, A.R., Workman, P., An evaluation of the ability of pifithrin-alpha and -beta to inhibit p53 function in two wild-type p53 human tumor cell lines. Mol. Cancer Ther. 4 (2005), 1369–1377.
126. Wang, L., Yu, Y., Chow, D.C., Yan, F., Hsu, C.C., Stossi, F., Mancini, M.A., Palzkill, T., Liao, L., Zhou, S., et al. Characterization of a steroid receptor coactivator small molecule stimulator that overstimulates cancer cells and leads to cell stress and death. Cancer Cell 28 (2015), 240–252.
127. Willems, L.I., Overkleeft, H.S., van Kasteren, S.I., Current developments in activity-based protein profiling. Bioconjug. Chem. 25 (2014), 1181–1191.
128. Williams, D.R., Ko, S.-K., Park, S., Lee, M.-R., Shin, I., An apoptosis-inducing small molecule that binds to heat shock protein 70. Angew. Chem. Int. Ed. 47 (2008), 7466–7469.
129. Winter, G.E., Buckley, D.L., Paulk, J., Roberts, J.M., Souza, A., Dhe-Paganon, S., Bradner, J.E., Phthalimide conjugation as a strategy for in vivo target protein degradation. Science 343 (2015), 1376–1381.
130. Workman, P., Collins, I., Probing the probes: fitness factors for small molecule tools. Chem. Biol. 17 (2010), 561–577.
131. Yap, T.A., Bjerke, L., Clarke, P.A., Workman, P., Drugging PI3K in cancer: refining targets and therapeutic strategies. Curr. Opin. Pharmacol. 23 (2015), 98–107.