1 pains pan-assay interference compounds -baell, j. b. and walters, m. a., nature 513, 481–483...

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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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Baell, J. B. and Walters, M. A., Nature 513, 481–483 (2014)

PAINS: Pan-assay interference compounds

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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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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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Baell, J. B. and Holloway, G. A. J. Med. Chem. 53, 2719–2740 (2010)

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PAINS Pan-assay interference compounds

1 pains pan-assay interference compounds -baell, j. b. and walters, m. a., nature 513, 481–483...

Documents

proteins pains

proteins alter proteins

proteins function

nm trap toxic

form aggregates

singlet oxygen redox

hydrogen peroxide

reactive metals