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Lead Optimization

Lead optimization is an operationally diverse stage of the drug discovery process in which the chemical structures of compounds or biologics are modified to improve target specificity and selectivity, plus pharmacodynamic, pharmacokinetic, and toxicological properties to produce a preclinical drug candidate. 

This process requires detailed characterization of lead compound series and lead biologics, including data related to toxicity, efficacy, stability, and bioavailability.

We offer analytical methods such as high-content analysis of cells with quantitative imaging systems and high-resolution compound-target binding analysis with biophysical technologies such as surface plasmon resonance. Our Cytiva cell models derived from human embryonic stem cells provide a biologically relevant tool for assessing toxic effects in, for example, heart cells, which might otherwise remain undetected. These methods are all used in conjunction with medicinal chemistry or protein engineering to optimize leads in order to improve aspects of performance without negatively impacting other aspects, such as increasing off-target effects.

Biacore SPR Systems IN Cell Analyzer HCA Systems Cytiva Cell Models Downloads

Biacore Surface Plasmon Resonance (SPR) Systems

Compounds

Compound-target binding rates (on- and off-rates) affect a lead compound's pharmacodynamic and pharmacokinetic properties. Kinetic assessment of a lead series using Biacore systems ensures selection of compounds on criteria that are relevant also for target binding (efficacy implications) and target selectivity (safety implications) in vivo.

Biotherapeutics

Label-free screening and characterization of biotherapeutic candidates using Biacore systems can readily accommodate early in vitro ADME-indicating analyses such as compound binding to multiple plasma proteins (% bound) and binding to liposomes of different compositions (fraction absorbed [Fa]). This ADME-indicating data can facilitate the early termination of unpromising candidates and the engineering of potential drugs to improve their pharmacokinetic properties.

IN Cell Analyzer High-Content Analysis (HCA) System

Early predictive toxicology tests on IN Cell Analyzer systems are increasingly used to progress leads. High-content analysis enables examination of cytotoxic effects at the individual cell level providing much greater insight into the mechanisms involved in a cytotoxic response. Many parameters from a broad range of sources can be studied: from simple genotoxicity assays to complex assays probing for cytotoxicity and from standard cellular assays to assays on model organisms such as zebra fish.

Cytiva Cardiomyocytes

Cardiotoxicity and hepatotoxicity are common causes of drug safety liabilities and withdrawal of drugs during development. Cytiva Cardiomyocytes are derived from NIH-approved human embryonic stem (hES) cells and provide an abundant and reliable source of biologically-relevant cells for cardiac safety and toxicity testing. The use of Cytiva Cardiomyocytes in lead optimization could facilitate the termination of unpromising compounds and the engineering of potential drug molecules to reduce the risk for toxic liabilities.

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