Critical review of the role of HTS in drug discovery

Macarrόn, Ricardo

doi:10.1016/j.drudis.2006.02.001

Cited by 224 publications

(156 citation statements)

References 17 publications

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“…20,21 The analysis of data generated in HTS has continuously evolved as the compound collections grew in size and chemical diversity; from the original simple activity-driven hit selection, HTS scientists today use more sophisticated methods and algorithms to enrich the chemical diversity of the output. There is, however, still room to better exploit the information that the HTS generates, in particular with the use of the single-shot data produced during the primary-screening campaigns.…”

Section: Discussionmentioning

confidence: 99%

Mining Natural-Products Screening Data for Target-Class Chemical Motifs

et al. 2014

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In this article, we describe two complementary data-mining approaches used to characterize the GlaxoSmithKline (GSK) natural-products set (NPS) based on information from the high-throughput screening (HTS) databases. Both methods rely on the aggregation and analysis of a large set of single-shot screening data for a number of biological assays, with the goal to reveal natural-product chemical motifs. One of them is an established method based on the data-driven clustering of compounds using a wide range of descriptors, 1 whereas the other method partitions and hierarchically clusters the data to identify chemical cores. 2,3 Both methods successfully find structural scaffolds that significantly hit different groups of discrete drug targets, compared with their relative frequency of demonstrating inhibitory activity in a large number of screens.We describe how these methods can be applied to unveil hidden information in large single-shot HTS data sets. Applied prospectively, this type of information could contribute to the design of new chemical templates for drug-target classes and guide synthetic efforts for lead optimization of tractable hits that are based on natural-product chemical motifs.Relevant findings for 7TM receptors (7TMRs), ion channels, class-7 transferases (protein kinases), hydrolases, and oxidoreductases will be discussed.

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Section: Discussionmentioning

confidence: 99%

Mining Natural-Products Screening Data for Target-Class Chemical Motifs

et al. 2014

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“…The solubility of recently discovered APIs is often very poor (Macarron, 2006;Vasconcelos et al, 2007) in the gastrointestinal fluids, resulting in low oral bioavailability (Wong et al, 2006). Methods that are available to eliminate the solubility problem (Fahr and Liu, 2007;Sarode et al, 2014) are either costly or their industrial applicability is limited .…”

Section: Introductionmentioning

confidence: 99%

Comparison of spray drying, electroblowing and electrospinning for preparation of Eudragit E and itraconazole solid dispersions

Sóti

Bocz

Pataki

et al. 2015

International Journal of Pharmaceutics

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Three solvent based methods: spray drying (SD), electrospinning (ES) and air-assisted electrospinning (electroblowing; EB) were used to prepare solid dispersions of itraconazole and Eudragit E. Samples with the same API/polymer ratios were prepared in order to make the three technologies comparable. The structure and morphology of solid dispersions were identified by scanning electron microscopy and solid phase analytical methods such as, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Raman chemical mapping. Moreover, the residual organic solvents of the solid products were determined by static headspace-gas chromatography/mass spectroscopy measurements and the wettability of samples was characterized by contact angle measurement. The pharmaceutical performance of the three dispersion type, evaluated by dissolution tests, proved to be very similar. According to XRPD and DSC analyses, made after the production, all the solid dispersions were free of any API crystal clusters but about 10 wt% drug crystallinity was observed after three months of storage in the case of the SD samples in contrast to the samples produced by ES and EB in which the polymer matrix preserved the API in amorphous state.

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“…Thus, the dissolution rate is required to achieve high bioavaibility of IBU. The dissolution rate could be improved by decreasing the particle size, leads to higher surface area of reaction [3][4][5][6][7]. It is very common that pharmaceutical technology uses the micronization process to reduce the particle size in order to increase the dissolution rate of drugs [8][9].…”

Section: Introductionmentioning

confidence: 99%

Enhancement of solubility and dissolution of ibuprofen microparticle prepared by ultrasonic spray drying

Rachmaniar¹,

Panatarani²,

Joni³

et al. 2017

mpj

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Ibuprofen (IBU) is one of the most commonly used nonsteroidal anti-inflammatory drugs with high permeability and low solubility. The aims of this research is to improve the solubility and dissolution of the IBU by reducing particle size using ultrasonic spray drying method and utilizing watersoluble polymer (polyvinyl alcohol (PVA)) and surfactant (sodium lauryl sulphate (SLS)) for particles formulation. The results showed that increasing amount of PVA, smaller particle size of as-prepared IBU-PVA-SLS was obtained, 6.3-fold smaller than untreated IBU. The in vitro drug release study for simulated gastric fluid without enzymes (0.1 N HCl or Buffer pH 1.2) shows the dissolution of prepared IBU-PVA-SLS significantly increase 2.4-fold higher than untreated IBU for dissolution time of 30 minutes. While the solubility of the IBU-PVA-SLS was increased 4.7-fold compare to untreated IBU. In general, IBU possessing relatively high dissolution in intestinal fluid. In contrast, the finding of recent investigation on dissolution of IBU-PVA-SLS is significantly increase in gastric fluid, either due to smaller particles size or PVA-SLS. Thus, despite the PVA and SLS determine the particles formation during polymerization yielding smaller particle size, they also responsible for effective drug delivery system. It was concluded that PVA and SLS in ultrasonic spray drying technique for IBU preparation successfully reduces the particle size and effectively enhances the solubility and dissolution rate of poorly water-soluble IBU in 0.1 N HCl.

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Critical review of the role of HTS in drug discovery

Cited by 224 publications

References 17 publications

Mining Natural-Products Screening Data for Target-Class Chemical Motifs

Mining Natural-Products Screening Data for Target-Class Chemical Motifs

Comparison of spray drying, electroblowing and electrospinning for preparation of Eudragit E and itraconazole solid dispersions

Enhancement of solubility and dissolution of ibuprofen microparticle prepared by ultrasonic spray drying

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