Pan-assay interference compounds (PAINS) that may not be too painful for chemical biology projects

Lagorce, David; Oliveira, Natacha; Villoutreix, Bruno O.

doi:10.1016/j.drudis.2017.05.017

Cited by 30 publications

(19 citation statements)

References 10 publications

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“…Recently, several studies have demonstrated the inability of PAINS alerts to filter-out promiscuous compounds and their oversensitivity, i.e., rejection of many of non-promiscuous compounds [ 36 , 37 ]. Removal of PAINS filters from the pipeline and their substitution by orthogonal assays [ 37 , 38 ] will greatly increase the attractiveness of chalcones as potential starting points in drug discovery.…”

Section: Design Of New Chalcone Derivativesmentioning

confidence: 99%

Chalcone Derivatives: Promising Starting Points for Drug Design

et al. 2017

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Medicinal chemists continue to be fascinated by chalcone derivatives because of their simple chemistry, ease of hydrogen atom manipulation, straightforward synthesis, and a variety of promising biological activities. However, chalcones have still not garnered deserved attention, especially considering their high potential as chemical sources for designing and developing new effective drugs. In this review, we summarize current methodological developments towards the design and synthesis of new chalcone derivatives and state-of-the-art medicinal chemistry strategies (bioisosterism, molecular hybridization, and pro-drug design). We also highlight the applicability of computer-assisted drug design approaches to chalcones and address how this may contribute to optimizing research outputs and lead to more successful and cost-effective drug discovery endeavors. Lastly, we present successful examples of the use of chalcones and suggest possible solutions to existing limitations.

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Section: Design Of New Chalcone Derivativesmentioning

confidence: 99%

Chalcone Derivatives: Promising Starting Points for Drug Design

et al. 2017

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“…In an effort to ameliorate the blind application of these filters, some authors have published data that question their usefulness. One finding which is crucial is the fact that many PAINs substructures can also be found in drugs available in the market [123, 124], meaning that if the filters are used without rational thinking, potentially good drug candidates can be disregarded. Phenotypic assays, which are regaining the value they used to have in the past for screening libraries of compounds since they take the biological setting as a whole, would be incredibly affected by the use of PAINs filters, preventing optimization of the structure, and again, leading to the loss of possible candidates [123].…”

Section: Main Textmentioning

confidence: 99%

The diverse mechanisms and anticancer potential of naphthoquinones

et al. 2019

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Cancer is one of the leading causes of death around the world and although the different clinical approaches have helped to increase survival rates, incidence is still high and so its mortality. Chemotherapy is the only approach which is systemic, reaching cancer cells in all body tissues and the search for new potent and selective drugs is still an attractive field within cancer research. Naphthoquinones, natural and synthetic, have garnered much attention in the scientific community due to their pharmacological properties, among them anticancer action, and potential therapeutic significance. Many mechanisms of action have been reported which also depend on structural differences among them. Here, we describe some of the most relevant mechanisms of action reported so far for naphthoquinones and highlight novel targets which are being described in the literature. Furthermore, we gather some of the most impressive efforts done by researchers to harness the anticancer properties of these compounds through specifically designed structural modifications.

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“…Therefore, a fit-for-purpose collection of filters for a screening collection requires more than a handful of specific assays using a single technology tested against a small number of compounds sharing a chemical feature, a common criticism of the original PAINS paper that has been recently backed by questioning many filters based on the analysis of the bioactivity profile of all compounds in PubChem. [23][24][25][26][27][28][29][30] In 2008, an analysis of frequent hitters in HTS campaigns conducted in GSK revealed 750 noisy compounds that had been subject to more than 13,000 dose-response experiments. Subsequently, we set out to measure the activity profile of every compound of the GSK HTS collection over hundreds of campaigns using the inhibitory frequency index (IFI), a pragmatic and intuitive measure of promiscuity.…”

Section: Introductionmentioning

confidence: 99%

Nuisance Compounds, PAINS Filters, and Dark Chemical Matter in the GSK HTS Collection

et al. 2018

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High-throughput screening (HTS) hits include compounds with undesirable properties. Many filters have been described to identify such hits. Notably, pan-assay interference compounds (PAINS) has been adopted by the community as the standard term to refer to such filters, and very useful guidelines have been adopted by the American Chemical Society (ACS) and subsequently triggered a healthy scientific debate about the pitfalls of draconian use of filters. Using an inhibitory frequency index, we have analyzed in detail the promiscuity profile of the whole GlaxoSmithKline (GSK) HTS collection comprising more than 2 million unique compounds that have been tested in hundreds of screening assays. We provide a comprehensive analysis of many previously published filters and newly described classes of nuisance structures that may serve as a useful source of empirical information to guide the design or growth of HTS collections and hit triaging strategies.

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Pan-assay interference compounds (PAINS) that may not be too painful for chemical biology projects

Cited by 30 publications

References 10 publications

Chalcone Derivatives: Promising Starting Points for Drug Design

Chalcone Derivatives: Promising Starting Points for Drug Design

The diverse mechanisms and anticancer potential of naphthoquinones

Nuisance Compounds, PAINS Filters, and Dark Chemical Matter in the GSK HTS Collection

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