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)
PAINS: Pan-assay interference compounds Baell, J. B. and Walters, M. A., Nature 513, 481–483 (2014)
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
PAINS: Pan-assay interference compounds Baell, J. B. et Al. Aust. J. Chem. 66, 1483–1494 (2013)
PAINS: Pan-assay interference compounds Baell, J. B. et Al. Aust. J. Chem. 66, 1483–1494 (2013)
PAINS: Pan-assay interference compounds Baell, J. B. et Al. Aust. J. Chem. 66, 1483–1494 (2013)
Frequent hitters (promiscuous compounds) Hu, Y. and Bajorath, J. AAPS J. 15, 808–815 (2013)
Frequent hitters (promiscuous compounds) Hu, Y. and Bajorath, J. AAPS J. 15, 808–815 (2013)
PAINS: Pan-assay interference compounds Baell, J. B. and Holloway, G. A. J. Med. Chem. 53, 2719–2740 (2010)
PAINS: Pan-assay interference compounds Baell, J. B. and Holloway, G. A. J. Med. Chem. 53, 2719–2740 (2010)
PAINS: Pan-assay interference compounds Baell, J. B. and Holloway, G. A. J. Med. Chem. 53, 2719–2740 (2010)
PAINS: Pan-assay interference compounds Baell, J. B. and Holloway, G. A. J. Med. Chem. 53, 2719–2740 (2010)
PAINS: Pan-assay interference compounds Baell, J. B. et Al. Aust. J. Chem. 66, 1483–1494 (2013)
PAINS: Pan-assay interference compounds Baell, J. B. et Al. Aust. J. Chem. 66, 1483–1494 (2013)
PAINS: Pan-assay interference compounds Baell, J. B. et Al. Aust. J. Chem. 66, 1483–1494 (2013)
Pan-assay interference compounds PAINS Pan-assay interference compounds