Rationale and benefit of using high throughput solubility screens in drug discovery

Goodwin, Joseph

doi:10.1016/j.ddtec.2005.03.001

Cited by 21 publications

(8 citation statements)

References 17 publications

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“…9) 2.1.5 Thermodynamic solubility: The thermodynamic solubility is often referred to as the solubility measured starting oŠ with a solid sample. 13,14,19) In this review, however, we do not use this term to avoid confusion.…”

Section: Apparent Solubilitymentioning

confidence: 94%

“…[7][8][9] 2.1.4 Kinetic solubility: The kinetic solubility has often been referred to as the solubility of a compound measured starting oŠ with a sample stock solution in a rich solvent, regardless of the incubation time (Section 5.2). 13,14) In this article, the kinetic solubility is deˆned as the concentration immediately after the addition of the concentrated sample stock solution into an aqueous media (typically within several minutes to 1-2 hours). [15][16][17][18] Therefore, the kinetic solubility represents the precipitation tendency.…”

Section: Apparent Solubilitymentioning

confidence: 99%

“…13,129,185,186) Following primary in vitro pharmacology screening, secondary in vitro pharmacology assay for selectivity, in vitro ADME assays, and in vitro toxicology assays are performed (Fig. 19).…”

Section: ‚ Strategies Of Solubility W Dissolution Assessment In Drugmentioning

confidence: 99%

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Solubility and Dissolution Profile Assessment in Drug Discovery

Sugano

Okazaki

Sugimoto

et al. 2007

Drug Metabolism and Pharmacokinetics

183

142

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The purposes of the review are to: a) Provide a comprehensible introduction of the-state-of-the-art sciences of solubility and dissolution, b) introduce typical technologies to assess solubility and dissolution, and c) propose the best practice strategy. The theories of solubility and dissolution required in drug discovery were reviewed especially from the view point of oral absorption. The physiological conditions in the gastrointestinal fluid in humans and animals were then briefly summarized. Technologies to assess solubility and dissolution in drug discovery were then introduced. Recently, these technologies have been improved by the laboratory automation and computational technologies. Finally, the strategies to apply these technologies for a drug discovery project were discussed.

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Section: Apparent Solubilitymentioning

confidence: 94%

Section: Apparent Solubilitymentioning

confidence: 99%

See 1 more Smart Citation

Solubility and Dissolution Profile Assessment in Drug Discovery

Sugano

Okazaki

Sugimoto

et al. 2007

Drug Metabolism and Pharmacokinetics

183

142

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show abstract

“…a less obvious problem that can plague cm is related to the sample solubility. 74,75,82,83,88,90,92 how much of the sample you have carefully weighed and tracked actually dissolves in buffer, and how much does that vary as it is tested in varying biological systems that may include variations in ph, protein and serum levels, detergent, or ionic strength? again, the answer is not yet clear, nor is there an industry standard, but more and more companies are realizing this source of error in both htS and lead optimization, where it is vital that accurate data are used to determine SaR as well as a structure-properties relationship (SpR) and make synthesis decisions.…”

Section: Chemical Errormentioning

confidence: 99%

Advances in Improving the Quality and Flexibility of Compound Management

Janzen¹,

Popa‐Burke²

2009

SLAS Discovery

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The process of drug discovery has evolved considerably since the advent of high-throughput screening (HTS) in the 1980s. Experts and opinion leaders today are agreeing that the current trend in the field is a focus on increasing overall quality (target, screening, and compounds), use of multiple screening approaches for lead discovery, and more flexibility in the process. The associated need for increased flexibility and quality control to support existing HTS paradigms as well as lower throughput approaches such as fragment screening, computational chemistry, focused library building, and centralized lead optimization support has required an evolution in compound management (CM, aka sample management or library management). Although there is much less published peer-reviewed data in CM, due to its historical links to HTS, it has followed very similar trends. In recent years, the focus in CM has been increasingly in compound quality and increased flexibility of the process, as opposed to number of compounds dispensed and speed of dispensing, which were standard metrics and indicators used not so long ago. Ideally, to screen the highest quality sample for every assay, one would start with a correct identity and pure solid, make a correct concentration solution in water or water-soluble/assay-compatible solvent that would allow 100% solubilization, and screen it immediately in a biological assay. Neither CM nor screening has advanced sufficiently to deliver this ideal scenario, but many significant advancements have been made in recent years both in terms of quality of compounds in stores and flexibility of the process, which will be reviewed herein.

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“…The aqueous solubility of a given chemical entity can be obtained by experimental determination, although this usually presents some difficulties [ 2 , 3 ]. The traditional “shake flask” assay for measuring solubility is an equilibrium (thermodynamical) assay in which the solid is mixed vigorously with an aqueous buffer for a long period of time.…”

Section: Introductionmentioning

confidence: 99%

QSPR Studies on Aqueous Solubilities of Drug-Like Compounds

Duchowicz

Castro

2009

IJMS

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A rapidly growing area of modern pharmaceutical research is the prediction of aqueous solubility of drug-sized compounds from their molecular structures. There exist many different reasons for considering this physico-chemical property as a key parameter: the design of novel entities with adequate aqueous solubility brings many advantages to preclinical and clinical research and development, allowing improvement of the Absorption, Distribution, Metabolization, and Elimination/Toxicity profile and “screenability” of drug candidates in High Throughput Screening techniques. This work compiles recent QSPR linear models established by our research group devoted to the quantification of aqueous solubilities and their comparison to previous research on the topic.

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Rationale and benefit of using high throughput solubility screens in drug discovery

Cited by 21 publications

References 17 publications

Solubility and Dissolution Profile Assessment in Drug Discovery

Solubility and Dissolution Profile Assessment in Drug Discovery

Advances in Improving the Quality and Flexibility of Compound Management

QSPR Studies on Aqueous Solubilities of Drug-Like Compounds

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