Seven Year Itch: Pan-Assay Interference Compounds (PAINS) in 2017-Utility and Limitations

被引：487

作者：

Baell, Jonathan B. ^{[1
,2
]}

Nissink, J. Willem M. ^{[3
]}

机构：

[1] Monash Univ, Monash Inst Pharmaceut Sci, Med Chem, Parkville, Vic 3052, Australia

[2] Nanjing Tech Univ, Sch Pharmaceut Sci, 30 South Puzhu Rd, Nanjing 211816, Jiangsu, Peoples R China

[3] AstraZeneca, IMED Biotech Unit, Computat Chem, Oncol, Unit 310,Cambridge Sci Pk,Milton Rd, Cambridge CB4 0WG, England

来源：

ACS CHEMICAL BIOLOGY | 2018年 / 13卷 / 01期

基金：

英国医学研究理事会;

关键词：

SCREENING METHOD; FALSE POSITIVES; CHEMICAL PROBES; DISCOVERY; LIBRARIES; ECSTASY; FILTERS; DESIGN; AGONY; HTS;

D O I：

10.1021/acschembio.7b00903

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Pan-Assay Interference Compounds (PAINS) are very familiar to medicinal chemists who have spent time fruitlessly trying to optimize these nonprogressible compounds. Electronic filters formulated to recognize PAINS can process hundreds and thousands of compounds in seconds and are in widespread current use to identify PAINS in order to exclude them from further analysis. However, this practice is fraught with danger because such black box treatment is simplistic. Here, we outline for the first time all necessary considerations for the appropriate use of PAINS filters.

引用

收藏

页码：36 / 44

页数：9

相关论文

共 32 条

[1]

The Ecstasy and Agony of Assay Interference Compounds [J].

Aldrich, Courtney ;

Bertozzi, Carolyn ;

Georg, Gunda I. ;

Kiessling, Laura ;

Lindsley, Craig ;

Liotta, Dennis ;

Merz, Kenneth M., Jr. ;

Schepartz, Manna ;

Wang, Shaomeng .

ACS MEDICINAL CHEMISTRY LETTERS, 2017, 8 (04) :379-382

[2]

The promise and peril of chemical probes [J].

Arrowsmith, Cheryl H. ;

Audia, James E. ;

Austin, Christopher ;

Baell, Jonathan ;

Bennett, Jonathan ;

Blagg, Julian ;

Bountra, Chas ;

Brennan, Paul E. ;

Brown, Peter J. ;

Bunnage, Mark E. ;

Buser-Doepner, Carolyn ;

Campbell, Robert M. ;

Carter, Adrian J. ;

Cohen, Philip ;

Copeland, Robert A. ;

Cravatt, Ben ;

Dahlin, Jayme L. ;

Dhanak, Dashyant ;

Edwards, Aled M. ;

Frye, Stephen V. ;

Gray, Nathanael ;

Grimshaw, Charles E. ;

Hepworth, David ;

Howe, Trevor ;

Huber, Kilian V. M. ;

Jin, Jian ;

Knapp, Stefan ;

Kotz, Joanne D. ;

Kruger, Ryan G. ;

Lowe, Derek ;

Mader, Mary M. ;

Marsden, Brian ;

Mueller-Fahrnow, Anke ;

Mueller, Susanne ;

O'Hagan, Ronan C. ;

Overington, John P. ;

Owen, Dafydd R. ;

Rosenberg, Saul H. ;

Roth, Brian ;

Ross, Ruth ;

Schapira, Matthieu ;

Schreiber, Stuart L. ;

Shoichet, Brian ;

Sundstrom, Michael ;

Superti-Furga, Giulio ;

Taunton, Jack ;

Toledo-Sherman, Leticia ;

Walpole, Chris ;

Walters, Michael A. ;

Willson, Timothy M. .

NATURE CHEMICAL BIOLOGY, 2015, 11 (08) :536-541

[3]

Chemical con artists foil drug discovery [J].

Baell, Jonathan ;

Walters, Michael A. .

NATURE, 2014, 513 (7519) :481-483

[4]

Feeling Nature's PAINS: Natural Products, Natural Product Drugs, and Pan Assay Interference Compounds (PAINS) [J].

Baell, Jonathan B. .

JOURNAL OF NATURAL PRODUCTS, 2016, 79 (03) :616-628

[5]

Screening-Based Translation of Public Research Encounters Painful Problems [J].

Baell, Jonathan B. .

ACS MEDICINAL CHEMISTRY LETTERS, 2015, 6 (03) :229-234

[6]

PAINS: Relevance to Tool Compound Discovery and Fragment-Based Screening [J].

Baell, Jonathan B. ;

Ferrins, Lori ;

Falk, Hendrik ;

Nikolakopoulos, George .

AUSTRALIAN JOURNAL OF CHEMISTRY, 2013, 66 (12) :1483-1494

[7]

Broad Coverage of Commercially Available Lead-like Screening Space with Fewer than 350,000 Compounds [J].

Baell, Jonathan B. .

JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2013, 53 (01) :39-55

[8]

Redox-active nuisance screening compounds and their classification [J].

Baell, Jonathan B. .

DRUG DISCOVERY TODAY, 2011, 16 (17-18) :840-841

[9]

Baell JB, 2010, FUTURE MED CHEM, V2, P1529, DOI [10.4155/fmc.10.237, 10.4155/FMC.10.237]

[10]

New Substructure Filters for Removal of Pan Assay Interference Compounds (PAINS) from Screening Libraries and for Their Exclusion in Bioassays [J].

Baell, Jonathan B. ;

Holloway, Georgina A. .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (07) :2719-2740

← 1 2 3 4 →