PAINS: Pan-assay interference compounds

PAINS
Pan-assay interference compounds
-Baell, J. B. and Walters, M. A., Nature 513, 481–483 (2014)
-Dahlin, J. L. & Walters, M. A. Future Med. Chem. 6, 1265–1290 (2014)
-Hu, Y. and Bajorath, J. AAPS J. 15, 808–815 (2013)
-Baell, J. B. et Al. Aust. J. Chem. 66, 1483–1494 (2013)
-Baell, J. B. and Holloway, G. A. J. Med. Chem. 53, 2719–2740 (2010)
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PAINS: Pan-assay interference compounds
Baell, J. B. and Walters, M. A., Nature 513, 481–483 (2014)
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PAINS: Pan-assay interference compounds
Possible false positive signal mechanisms:
- Form aggregates
- Absorb or emit light at relevant wavelengths (λex = 680 nm or λem = 520-620 nm)
- Trap toxic or reactive metals used to synthesize molecules
- Sequester metal ions that are essential to a protein’s function
- React with singlet oxygen
- Redox cyclers: produce hydrogen peroxide, which inactivates the target
protein and makes the compound look like a good inhibitor
- Are inherently “sticky” and can bind to many sites on proteins
- Alter proteins chemically without fitting specifically into a binding site
- Covalently bind to proteins
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PAINS: Pan-assay interference compounds
Baell, J. B. et Al. Aust. J. Chem. 66, 1483–1494 (2013)
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PAINS: Pan-assay interference compounds
Baell, J. B. et Al. Aust. J. Chem. 66, 1483–1494 (2013)
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PAINS: Pan-assay interference compounds
Baell, J. B. et Al. Aust. J. Chem. 66, 1483–1494 (2013)
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Frequent hitters (promiscuous compounds)
Hu, Y. and Bajorath, J. AAPS J. 15, 808–815 (2013)
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Frequent hitters (promiscuous compounds)
Hu, Y. and Bajorath, J. AAPS J. 15, 808–815 (2013)
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PAINS: Pan-assay interference compounds
Baell, J. B. and Holloway, G. A. J. Med. Chem. 53, 2719–2740 (2010)
9
PAINS: Pan-assay interference compounds
Baell, J. B. and Holloway, G. A. J. Med. Chem. 53, 2719–2740 (2010)
10
PAINS: Pan-assay interference compounds
Baell, J. B. and Holloway, G. A. J. Med. Chem. 53, 2719–2740 (2010)
11
PAINS: Pan-assay interference compounds
Baell, J. B. and Holloway, G. A. J. Med. Chem. 53, 2719–2740 (2010)
12
PAINS: Pan-assay interference compounds
Baell, J. B. et Al. Aust. J. Chem. 66,
1483–1494 (2013)
13
PAINS: Pan-assay interference compounds
Baell, J. B. et Al. Aust. J. Chem. 66, 1483–1494 (2013)
14
PAINS: Pan-assay interference compounds
Baell, J. B. et Al. Aust. J. Chem. 66, 1483–1494 (2013)
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PAINS
Pan-assay interference compounds
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