Assessing the ability of chemical similarity measures to discriminate between active and inactive compounds

Delaney, John S.

doi:10.1007/bf01715525

Cited by 50 publications

(46 citation statements)

References 3 publications

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“…TheT animoto coefficient is am easure of the similarity of different fingerprints, ranging from zero for no similarity to one for identical structures. [36] An ovel two-dimensional scaffold fingerprint (SFP) was presented by Rabal et al [37] for mining ring fragments (Figure 2). This method not only encodes the usual 2D and 3D descriptors,s uch as shape,t opology,h eteroatoms,b ridges, spirocyclic centers,d iversity points,s p 3 carbon atoms,a nd chirality,b ut also pharmacophoric features,s uch as the number of hydrogen-bond donors and acceptors and their relative orientation (vectors), as they play ac ritical role in drug discovery.S FP can be used 1) to identify alternative chemotypes,including bioisosteres,toareference ring either in avisual mode or by running quantitative similarity searches and 2) in chemotype-based diversity selection.…”

Section: Scaffolds and Scaffold Diversitymentioning

confidence: 98%

Scaffold Diversity Synthesis and Its Application in Probe and Drug Discovery

et al. 2016

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Scaffold diversity is a crucial feature of compound collections that has a huge impact on their success in biological screenings. The synthesis of highly complex and diverse scaffolds, which could be based on natural products, for example, is an arduous task that requires expertise in various aspects of organic synthesis and structural analysis. This challenge has been addressed by a number of synthesis designs, which employ natural products as a source of scaffold diversity, transform suitably designed common intermediates into various molecular frameworks, or entail highly concise synthetic routes to a number of distinct and complex scaffolds. In this Minireview, we highlight recent synthetic developments towards the construction of diverse and complex scaffolds and the application of the resulting compound collections in drug and probe discovery.

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Section: Scaffolds and Scaffold Diversitymentioning

confidence: 98%

Scaffold Diversity Synthesis and Its Application in Probe and Drug Discovery

et al. 2016

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“…If a set bit is considered as a feature present in the molecule, the Tanimoto coefficient is a measure of the number of common features in both molecules (31). A Tanimoto coefficient of >0.85 indicates that two molecules have similar activities (32).…”

Section: Methodsmentioning

confidence: 99%

SuperHapten: a comprehensive database for small immunogenic compounds

Günther

Hempel

Dunkel

et al. 2007

Nucleic Acids Research

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The immune system protects organisms from foreign proteins, peptide epitopes and a multitude of chemical compounds. Among these, haptens are small molecules, eliciting an immune response when conjugated with carrier molecules. Known haptens are xenobiotics or natural compounds, which can induce a number of autoimmune diseases like contact dermatitis or asthma. Furthermore, haptens are utilized in the development of biosensors, immunomodulators and new vaccines. Although hapten-induced allergies account for 6–10% of all adverse drug effects, the understanding of the correlation between structural and haptenic properties is rather fragmentary. We have developed a manually curated hapten database, SuperHapten, integrating information from literature and web resources. The current version of the database compiles 2D/3D structures, physicochemical properties and references for about 7500 haptens and 25,000 synonyms. The commercial availability is documented for about 6300 haptens and 450 related antibodies, enabling experimental approaches on cross-reactivity. The haptens are classified regarding their origin: pesticides, herbicides, insecticides, drugs, natural compounds, etc. Queries allow identification of haptens and associated antibodies according to functional class, carrier protein, chemical scaffold, composition or structural similarity. SuperHapten is available online at .

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“…Other studies have been carried out using high-throughput screening data sets to analyze the relationship between active and inactive compounds in light of their calculated similarity values [34,37,38]. These studies have illustrated that generally applicable similarity threshold values are not available as bioactivity markers and have highlighted the "0.85 myth".…”

Section: Intrinsic Caveatsmentioning

confidence: 97%

Advanced Fingerprint Methods for Similarity Searching: Balancing Molecular Complexity Effects

Wang¹,

Bajorath²

2010

CCHTS

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Fingerprint representations of molecular structure and properties were among the first computational tools for similarity searching and are widely applied to this date, which is in part due to their computational efficiency and ease-of-use. Moreover, despite their simplicity, 2D molecular fingerprints have been surprisingly successful in identifying novel active compounds. However, properly applying 2D fingerprint representations and similarity metrics in the search for active molecules is much more complicated than one might assume. For example, no generally applicable similarity functions and threshold values exist that reliably indicate a level of molecular similarity that results in similar biological activity. Furthermore, fingerprint search calculations are known to be biased by molecular size and complexity effects, which often lead to a significant increase in false-positive rates. In this contribution, we will describe known caveats associated with fingerprint similarity searching and strategies to overcome these difficulties including the design of complexity-independent fingerprint representations and similarity metrics.

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Assessing the ability of chemical similarity measures to discriminate between active and inactive compounds

Cited by 50 publications

References 3 publications

Scaffold Diversity Synthesis and Its Application in Probe and Drug Discovery

Scaffold Diversity Synthesis and Its Application in Probe and Drug Discovery

SuperHapten: a comprehensive database for small immunogenic compounds

Advanced Fingerprint Methods for Similarity Searching: Balancing Molecular Complexity Effects

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