Transcript 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. -Hu, Y. and Bajorath, J.
Future Med. Chem.
AAPS J.
6, 1265 –1290 (2014) 15, 808 –815 (2013) -Baell, J. B.
et Al
.
Aust. J. Chem.
-Baell, J. B. and Holloway, G. A. 66, 1483 –1494 (2013)
J. Med. Chem.
53, 2719 –2740 (2010) 1
PAINS: Pan-assay interference compounds
Baell, J. B. and Walters, M. A.,
Nature
513, 481 –483 (2014) 2
PAINS: Pan-assay interference compounds
Possible false positive signal mechanisms: - Form aggregates - Absorb or emit light at relevant wavelengths ( λ ex = 680 nm or λ em = 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 3
PAINS: Pan-assay interference compounds
Baell, J. B.
et Al
.
Aust. J. Chem.
66, 1483 –1494 (2013) 4
PAINS: Pan-assay interference compounds
Baell, J. B.
et Al
.
Aust. J. Chem.
66, 1483 –1494 (2013) 5
PAINS: Pan-assay interference compounds
Baell, J. B.
et Al
.
Aust. J. Chem.
66, 1483 –1494 (2013) 6
Frequent hitters (promiscuous compounds)
Hu, Y. and Bajorath, J.
AAPS J.
15, 808 –815 (2013) 7
Frequent hitters (promiscuous compounds)
Hu, Y. and Bajorath, J.
AAPS J.
15, 808 –815 (2013) 8
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.
1483 –1494 (2013) 66, 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) 15
PAINS
Pan-assay interference compounds
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