“Plate Cherry Picking”: A Novel Semi-Sequential Screening Paradigm for Cheaper, Faster, Information-Rich Compound Selection

Crisman, Thomas J.; Jenkins, Jeremy L.; Parker, Christian N.; Hill, William A.; Bender, Andreas; Deng, Zhenghong; Nettles, James H.; Davies, John W.; Glick, Meir

doi:10.1177/1087057107299427

Cited by 34 publications

(28 citation statements)

References 34 publications

(38 reference statements)

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“…The parameters for scaffold generation were similar to those used in our previous work 13 ; in particular, different elemental atom types in the ring systems were treated as distinct features. The number of unique Murcko scaffolds in a given plate was then used to measure the plate diversity.…”

Section: Generating Murcko Scaffoldsmentioning

confidence: 99%

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Plate-Based Diversity Selection Based on Empirical HTS Data to Enhance the Number of Hits and Their Chemical Diversity

Sukuru¹,

Jenkins²,

Beckwith

et al. 2009

SLAS Discovery

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Section: Generating Murcko Scaffoldsmentioning

confidence: 99%

“…In our previous work, 13 we described a plate-based diversity selection method, based on Murcko scaffolds, to select a mediumsized subset of the screening deck. The objective was to select the combination of in-house plates that would maximize the diversity, defined by the number of unique Murcko scaffolds, in the selected subset.…”

mentioning

confidence: 99%

Plate-Based Diversity Selection Based on Empirical HTS Data to Enhance the Number of Hits and Their Chemical Diversity

Sukuru¹,

Jenkins²,

Beckwith

et al. 2009

SLAS Discovery

Self Cite

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“…9,10 Beginning in 2006, a novel form of subset screening coined plate-based diversity screening (PBDS) was developed and implemented in Pfizer. 11 Novartis reported on similar implementations in 2007 12 and 2009. 13 The PBDS offers a unique approach in that the screening subset was constructed by plate selection as opposed to cherry-picking individual compounds.…”

Section: Introductionmentioning

confidence: 99%

“…Novartis first used Murcko frames and chemical fingerprints to quantify the coverage of space in their reports of a platebase diversity selection. 12,13 Pfizer used a cell-based method to quantify the coverage in lower dimension BCUTs 23,24 chemistry space for diverse subset 10 and earlier generations of PBDS subsets. 11,14 In this report, the ECFP4 fingerprints-based similarity is used to determine the overall diversity of the compound collection.…”

Section: Metric For Diversity Of Platesmentioning

confidence: 99%

A Heuristic Algorithm for Plate SelectionThat Maximizes Compound Diversity

Zhu¹,

Klug-McLeod²,

Bakken³

2013

Croat. Chem. Acta

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Abstract. A heuristic algorithm was developed to maximize compound diversity within a subset of screening plates used in high throughput screening (HTS) to initiate the drug discovery process. The approach overcame the challenge of combinatorial explosion for selecting plate subsets with maximum compound diversity. The method yielded novel forms of plate-based diversity subsets (PBDS) for HTS screening in lead discovery. The algorithm, its validation and the application to our screening collection are outlined.

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“…These large libraries cover only a small fraction of chemical space, which may hinder the discovery of inhibitors for targets with unusual binding sites such as allosteric sites or protein-protein interactions (PPIs). To reduce the cost of HTS, new strategies involving smaller numbers of diverse compounds are being sought (Crisman et al, 2007;Zhu et al, 2013;Nissink et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

The potential use of single-particle electron microscopy as a tool for structure-based inhibitor design

Rawson

McPhillie

Johnson

et al. 2017

Acta Cryst Sect D Struct Biol

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Recent developments in electron microscopy (EM) have led to a step change in our ability to solve the structures of previously intractable systems, especially membrane proteins and large protein complexes. This has provided new opportunities in the field of structure-based drug design, with a number of highprofile publications resolving the binding sites of small molecules and peptide inhibitors. There are a number of advantages of EM over the more traditional X-ray crystallographic approach, such as resolving different conformational states and permitting the dynamics of a system to be better resolved when not constrained by a crystal lattice. There are still significant challenges to be overcome using an EM approach, not least the speed of structure determination, difficulties with low-occupancy ligands and the modest resolution that is available. However, with the anticipated developments in the field of EM, the potential of EM to become a key tool for structure-based drug design, often complementing X-ray and NMR studies, seems promising.

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“Plate Cherry Picking”: A Novel Semi-Sequential Screening Paradigm for Cheaper, Faster, Information-Rich Compound Selection

Cited by 34 publications

References 34 publications

Plate-Based Diversity Selection Based on Empirical HTS Data to Enhance the Number of Hits and Their Chemical Diversity

Plate-Based Diversity Selection Based on Empirical HTS Data to Enhance the Number of Hits and Their Chemical Diversity

A Heuristic Algorithm for Plate SelectionThat Maximizes Compound Diversity

The potential use of single-particle electron microscopy as a tool for structure-based inhibitor design

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