PAINS: Pan-assay interference compounds

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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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