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HIGH THROUGHPUT SCREENING (HTS)

PRESENTED BY: IQRAR AHMAD (M.PHARM SECOND SEMESTER)

DEPARTMENT OF PHARMACEUTICAL CHEMISTRY

R.C PATEL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH,SHIRPUR

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HIGH THROUGHPUT SCREENING (HTS)

HTS is process by which large number of compounds are rapidly tested for their

ability to modify the properties of a selected biological target.

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INTRODUCTION

High Throughput Screening (HTS) is a

drug-discovery process widely used in the

pharmaceutical industry. It leverages

automation to quickly assay the biological

or biochemical activity of a large number

of drug-like compounds.

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It is a useful for discovering ligands for

receptors, enzymes, ion-channels or other

pharmacological targets, or pharmacologically

profiling a cellular or biochemical pathway of

interest.

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GOAL OF HTS

Goal is to identify ‘hits’ or ‘leads’ - affect target in desired manner active at fairly low concenteration ( more likely to

show specificity) - new structure HTS = 50,000-100,000 compounds screened per

day!!!

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DETECTION METHODS IN HTS:

• Spectroscopy

• Mass Spectrometry

• Chromatography

• Calorimetry

• X-ray diffraction

• Microscopy

• Radioactive methods

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SPECTROSCOPY IN HTS:

• Fluorescence Spectroscopy

• Total internal reflection fluorescence (TIRF)

• Nuclear magnetic resonance (NMR)

• Absorption and luminescence sp.

• Fourier transformed infrared sp. (FTIR)

• Light scattering

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CHROMATOGRAPHY IN HTS:

• Gas chromatography (GC)

• Thin layer chromatography

• Liquid chromatography (HPLC)

• Ion Exchange chromatography

• Reverse phase chromatography

• Hydrophobic interaction chromatography

• Affinity chromatography

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CALORIMETRY IN HTS:

• Isothermal titration Calorimetry (ITC)• Differential scanning Calorimetry (DSC)

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ADVANTAGES OF HTS High sensitivity of assay (single molecule detection)

High speed of assay (automation)

Fast data processing of results

Reproducibility

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DISADVANTAGES: High cost

Low data quality

Local contamination

Need of relatively pure product

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USES OF HTS: To screen for all kind of novel biological active compounds

(libraries): • Natural products• Combinatorial Libraries (peptides, chemicals…)• Biological libraries

To screen Micro arrays such as:• DNA chips• RNA chips• Protein chips

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NEWER METHOD IN HTS:

High-Throughput, Fluorescence-Based Screening

For screening, expressed proteins are labelled

either as fusions with green fluorescent protein (GFP)or

through translational incorporation of a fluorescent amino

acid derivative, BODIPY-FL-Lysine.

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REFRENCES:1. “Medicnal chemistry” by ashutosh kar fifth revised

and expanded edition new age international publication,reprint 2011

2. Review On: High-Throughput Screening Is An Approach To Drug Discovery by Ashok A. Hajare, Sachin S. American Journal Of Pharmatech Research

3. Text book of Lead Generation Approaches In Drug Discovery by Zoran Rankovic

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